Publications

TitleAbstractYear(sorted ascending)
Filter
PMID
Filter
mechanism of oxidant-induced mistranslation by threonyl-trna synthetase.aminoacyl-trna synthetases maintain the fidelity during protein synthesis by selective activation of cognate amino acids at the aminoacylation site and hydrolysis of misformed aminoacyl-trnas at the editing site. threonyl-trna synthetase (thrrs) misactivates serine and utilizes an editing site cysteine (c182 in escherichia coli) to hydrolyze ser-trna(thr). hydrogen peroxide oxidizes c182, leading to ser-trna(thr) production and mistranslation of threonine codons as serine. the mechanism of c182 ...201424744241
purification, crystallization and preliminary crystallographic analysis of a ribosome-recycling factor from thermoanaerobacter tengcongensis (tterrf).ribosome-recycling factor (rrf) plays an essential role in the fourth step of protein synthesis in prokaryotes. rrf combined with elongation factor g (ef-g) disassembles the post-termination ribosome complex and recycles the protein synthesis machine for the next round of translation. a reductive-methylation-modified rrf from thermoanaerobacter tengcongensis (tterrf) has been crystallized using the vapour-diffusion method. the crystal grew in a condition consisting of 0.1 m citric acid ph 3.5, 3 ...201424817715
binding and channeling of alternative substrates in the enzyme dmpfg: a molecular dynamics study.dmpfg is a bifunctional enzyme comprised of an aldolase subunit, dmpg, and a dehydrogenase subunit, dmpf. the aldehyde intermediate produced by the aldolase is channeled directly through a buried molecular channel in the protein structure from the aldolase to the dehydrogenase active site. in this study, we have investigated the binding of a series of progressively larger substrates to the aldolase, dmpg, using molecular dynamics. all substrates investigated are easily accommodated within the ac ...201424739167
the transmembrane channel-like protein family and human papillomaviruses: insights into epidermodysplasia verruciformis and progression to squamous cell carcinoma.epidermodysplasia verruciformis (ev) is a rare genodermatosis characterized by increased sensitivity to infection by the β-subtype of human papillomaviruses (β-hpvs), causing persistent, tinea versicolor-like dermal lesions. in a majority of affected individuals, these macular lesions progress to invasive cutaneous squamous cell carcinoma (cscc) in sun-exposed areas. while mutations in transmembrane channel-like 6 (tmc6 / ever1) and 8 (tmc8 / ever2) have been causally linked to ev, their molecul ...201424800179
metal specificity of cyanobacterial nickel-responsive repressor inrs: cells maintain zinc and copper below the detection threshold for inrs.inrs is a ni(ii)-responsive, csor/rcnr-like, dna-binding transcriptional repressor of the nrsd gene, but the ni(ii) co-ordination sphere of inrs is unlike ni(ii)-rcnr. we show that copper and zn(ii) also bind tightly to inrs and in vitro these ions also impair inrs binding to the nrsd operator-promoter. inrs does not respond to zn(ii) (or copper) in vivo after 48 h, when zn(ii) sensor ziar responds, but inrs transiently responds (1 h) to both metals. inrs conserves only one (of two) second co-or ...201424666373
crystal structures of the structure-selective nuclease mus81-eme1 bound to flap dna substrates.the mus81-eme1 complex is a structure-selective endonuclease with a critical role in the resolution of recombination intermediates during dna repair after interstrand cross-links, replication fork collapse, or double-strand breaks. to explain the molecular basis of 3' flap substrate recognition and cleavage mechanism by mus81-eme1, we determined crystal structures of human mus81-eme1 bound to various flap dna substrates. mus81-eme1 undergoes gross substrate-induced conformational changes that re ...201424733841
diversity of the metal-transporting p1b-type atpases.the p1b-atpases are integral membrane proteins that couple atp hydrolysis to metal cation transport. widely distributed across all domains of life, these enzymes have been previously shown to transport copper, zinc, cobalt, and other thiophilic heavy metals. recent data suggest that these enzymes may also be involved in nickel and/or iron transport. here we have exploited large amounts of genomic data to examine and classify the various p1b-atpase subfamilies. specifically, we have combined new ...201424729073
biochemical aspects of bacterial strategies for handling the incomplete translation processes.during protein synthesis in cells, translating ribosomes may encounter abnormal situations that lead to retention of immature peptidyl-trna on the ribosome due to failure of suitable termination processes. bacterial cells handle such situations by employing three systems that rescue the stalled translation machinery. the transfer messenger rna/small protein b (tmrna/smpb) system, also called the trans-translation system, rescues stalled ribosomes by initiating template switching from the incompl ...201424782856
molecular recognition and modification of the 30s ribosome by the aminoglycoside-resistance methyltransferase npma.aminoglycosides are potent, broad spectrum, ribosome-targeting antibacterials whose clinical efficacy is seriously threatened by multiple resistance mechanisms. here, we report the structural basis for 30s recognition by the novel plasmid-mediated aminoglycoside-resistance rrna methyltransferase a (npma). these studies are supported by biochemical and functional assays that define the molecular features necessary for npma to catalyze m(1)a1408 modification and confer resistance. the requirement ...201424717845
rna epigenetics.mammalian messenger rna (mrna) and long noncoding rna (lncrna) contain tens of thousands of posttranscriptional chemical modifications. among these, the n(6)-methyl-adenosine (m(6)a) modification is the most abundant and can be removed by specific mammalian enzymes. m(6)a modification is recognized by families of rna binding proteins that affect many aspects of mrna function. mrna/lncrna modification represents another layer of epigenetic regulation of gene expression, analogous to dna methylati ...201424768686
rna epigenetics.mammalian messenger rna (mrna) and long noncoding rna (lncrna) contain tens of thousands of posttranscriptional chemical modifications. among these, the n(6)-methyl-adenosine (m(6)a) modification is the most abundant and can be removed by specific mammalian enzymes. m(6)a modification is recognized by families of rna binding proteins that affect many aspects of mrna function. mrna/lncrna modification represents another layer of epigenetic regulation of gene expression, analogous to dna methylati ...201424768686
polyamines in response to abiotic stress tolerance through transgenic approaches.the distribution, growth, development and productivity of crop plants are greatly affected by various abiotic stresses. worldwide, sustainable crop productivity is facing major challenges caused by abiotic stresses by reducing the potential yield in crop plants by as much as 70%. plants can generally adapt to one or more environmental stresses to some extent. physiological and molecular studies at transcriptional, translational, and transgenic plant levels have shown the pronounced involvement o ...201424710064
the substrate specificity, enantioselectivity and structure of the (r)-selective amine : pyruvate transaminase from nectria haematococca.during the last decade the use of transaminases for the production of pharmaceutical and fine chemical intermediates has attracted a great deal of attention. transaminases are versatile biocatalysts for the efficient production of amine intermediates and many have (s)-enantiospecificity. transaminases with (r)-specificity are needed to expand the applications of these enzymes in biocatalysis. in this work we have identified a fungal putative (r)-specific transaminase from the eurotiomycetes nect ...201424618038
the old and new testaments of gene regulation. evolution of multi-subunit rna polymerases and co-evolution of eukaryote complexity with the rnap ii ctd.i relate a story of genesis told from the point of view of multi-subunit rna polymerases (rnaps) including an old testament (core rnap motifs in all cellular life) and a new testament (the rnap ii heptad repeat carboxy terminal domain (ctd) and ctd interactome in eukarya). the old testament: at their active site, one class of eukaryotic interfering rnap and ubiquitous multi-subunit rnaps each have two-double psi β barrel (dpbb) motifs (a distinct pattern for compact 6-β sheet barrels). between β ...201425764332
tmrna-mediated trans-translation as the major ribosome rescue system in a bacterial cell.transfer messenger rna (tmrna; also known as 10sa rna or ssra rna) is a small rna molecule that is conserved among bacteria. it has structural and functional similarities to trna: it has an upper half of the trna-like structure, its 5' end is processed by rnase p, it has typical trna-specific base modifications, it is aminoacylated with alanine, it binds to ef-tu after aminoacylation and it enters the ribosome with ef-tu and gtp. however, tmrna lacks an anticodon, and instead it has a coding seq ...201424778639
design of activated serine-containing catalytic triads with atomic-level accuracy.a challenge in the computational design of enzymes is that multiple properties, including substrate binding, transition state stabilization and product release, must be simultaneously optimized, and this has limited the absolute activity of successful designs. here, we focus on a single critical property of many enzymes: the nucleophilicity of an active site residue that initiates catalysis. we design proteins with idealized serine-containing catalytic triads and assess their nucleophilicity dir ...201424705591
characterization of the type 2 nadh:menaquinone oxidoreductases from staphylococcus aureus and the bactericidal action of phenothiazines.methicillin-resistant staphylococcus aureus (mrsa) is currently one of the principal multiple drug resistant bacterial pathogens causing serious infections, many of which are life-threatening. consequently, new therapeutic targets are required to combat such infections. in the current work, we explore the type 2 nicotinamide adenine dinucleotide reduced form (nadh) dehydrogenases (ndh-2s) as possible drug targets and look at the effects of phenothiazines, known to inhibit ndh-2 from mycobacteriu ...201424709059
off-resonance rotating-frame relaxation dispersion experiment for 13c in aromatic side chains using l-optimized trosy-selection.protein dynamics on the microsecond-millisecond time scales often play a critical role in biological function. nmr relaxation dispersion experiments are powerful approaches for investigating biologically relevant dynamics with site-specific resolution, as shown by a growing number of publications on enzyme catalysis, protein folding, ligand binding, and allostery. to date, the majority of studies has probed the backbone amides or side-chain methyl groups, while experiments targeting other sites ...201424706175
trna synthetase: trna aminoacylation and beyond.the aminoacyl-trna synthetases are prominently known for their classic function in the first step of protein synthesis, where they bear the responsibility of setting the genetic code. each enzyme is exquisitely adapted to covalently link a single standard amino acid to its cognate set of trna isoacceptors. these ancient enzymes have evolved idiosyncratically to host alternate activities that go far beyond their aminoacylation role and impact a wide range of other metabolic pathways and cell sign ...201424706556
thermodynamic and kinetic insights into stop codon recognition by release factor 1.stop codon recognition is a crucial event during translation termination and is performed by class i release factors (rf1 and rf2 in bacterial cells). recent crystal structures showed that stop codon recognition is achieved mainly through a network of hydrogen bonds and stacking interactions between the stop codon and conserved residues in domain ii of rf1/rf2. additionally, previous studies suggested that recognition of stop codons is coupled to proper positioning of rf1 on the ribosome, which ...201424699820
biosynthesis and functions of sulfur modifications in trna.sulfur is an essential element for a variety of cellular constituents in all living organisms. in trna molecules, there are many sulfur-containing nucleosides, such as the derivatives of 2-thiouridine (s(2)u), 4-thiouridine (s(4)u), 2-thiocytidine (s(2)c), and 2-methylthioadenosine (ms(2)a). earlier studies established the functions of these modifications for accurate and efficient translation, including proper recognition of the codons in mrna or stabilization of trna structure. in many cases, ...201424765101
evidence of positive selection in mitochondrial complexes i and v of the african elephant.as species evolve, they become adapted to their local environments. detecting the genetic signature of selection and connecting that to the phenotype of the organism, however, is challenging. here we report using an integrative approach that combines dna sequencing with structural biology analyses to assess the effect of selection on residues in the mitochondrial dna of the two species of african elephants. we detected evidence of positive selection acting on residues in complexes i and v, and w ...201424695069
crystal structure of saccharomyces cerevisiae mitochondrial gatfab reveals a novel subunit assembly in trna-dependent amidotransferases.yeast mitochondrial gln-mtrnagln is synthesized by the transamidation of mischarged glu-mtrnagln by a non-canonical heterotrimeric trna-dependent amidotransferase (adt). the gata and gatb subunits of the yeast adt (gatfab) are well conserved among bacteria and eukaryota, but the gatf subunit is a fungi-specific ortholog of the gatc subunit found in all other known heterotrimeric adts (gatcab). here we report the crystal structure of yeast mitochondrial gatfab at 2.0 å resolution. the c-terminal ...201424692665
the mtha mutation conferring low-level resistance to streptomycin enhances antibiotic production in bacillus subtilis by increasing the s-adenosylmethionine pool size.certain str(r) mutations that confer low-level streptomycin resistance result in the overproduction of antibiotics by bacillus subtilis. using comparative genome-sequencing analysis, we successfully identified this novel mutation in b. subtilis as being located in the mtha gene, which encodes s-adenosylhomocysteine/methylthioadenosine nucleosidase, an enzyme involved in the s-adenosylmethionine (sam)-recycling pathways. transformation experiments showed that this mtha mutation was responsible fo ...201424509311
h(2)o(2) production in species of the lactobacillus acidophilus group: a central role for a novel nadh-dependent flavin reductase.hydrogen peroxide production is a well-known trait of many bacterial species associated with the human body. in the presence of oxygen, the probiotic lactic acid bacterium lactobacillus johnsonii ncc 533 excretes up to 1 mm h(2)o(2), inducing growth stagnation and cell death. disruption of genes commonly assumed to be involved in h(2)o(2) production (e.g., pyruvate oxidase, nadh oxidase, and lactate oxidase) did not affect this. here we describe the purification of a novel nadh-dependent flavin ...201424487531
helix capping in rna structure.helices are an essential element in defining the three-dimensional architecture of structured rnas. while internal basepairs in a canonical helix stack on both sides, the ends of the helix stack on only one side and are exposed to the loop side, thus susceptible to fraying unless they are protected. while coaxial stacking has long been known to stabilize helix ends by directly stacking two canonical helices coaxially, based on analysis of helix-loop junctions in rna crystal structures, herein we ...201424691270
function and evolution of the sox multienzyme complex in the marine gammaproteobacterium congregibacter litoralis.core sets of sox genes were detected in several genome sequenced members of the environmental important om60/nor5 clade of marine gammaproteobacteria. however, emendation of media with thiosulfate did not result in stimulation of growth in two of these strains and cultures of congregibacter litoralis dsm 17192(t) did not oxidize thiosulfate to sulfate in concentrations of one mmol l(-1) or above. on the other hand, a significant production of sulfate was detected upon growth with the organic sul ...201425006520
understanding the mechanism of proteasome 20s core particle gating.the 20s core particle proteasome is a molecular machine playing an important role in cellular function by degrading protein substrates that no longer are required or that have become damaged. regulation of proteasome activity occurs, in part, through a gating mechanism controlling the sizes of pores at the top and bottom ends of the symmetric proteasome barrel and restricting access to catalytic sites sequestered in the lumen of the structure. although atomic resolution models of both open and c ...201424706783
the hica toxin from burkholderia pseudomallei has a role in persister cell formation.ta (toxin-antitoxin) systems are widely distributed amongst bacteria and are associated with the formation of antibiotic tolerant (persister) cells that may have involvement in chronic and recurrent disease. we show that overexpression of the burkholderia pseudomallei hica toxin causes growth arrest and increases the number of persister cells tolerant to ciprofloxacin or ceftazidime. furthermore, our data show that persistence towards ciprofloxacin or ceftazidime can be differentially modulated ...201424502667
synthesis of water-soluble dinuclear mn-porphyrin with multiple antioxidative activities.superoxide dismutase (sod) and catalase activities of a drug are of great importance for its effective protection against reactive oxygen species (ros)-induced injury. achievement of catalase activity of a synthetic compound remains a challenge. water-soluble mn-porphyrins have high sod and peroxynitrite (onoo(-)) reducing activities, but not catalase-like activity. herein, we are able to retain the fair sod-like activity of a mononuclear mn-5-(n-methylpyridinium-4-yl)-10,15,20-triphenyl porphyr ...201424944735
bacteriophage λ n protein inhibits transcription slippage by escherichia coli rna polymerase.transcriptional slippage is a class of error in which ribonucleic acid (rna) polymerase incorporates nucleotides out of register, with respect to the deoxyribonucleic acid (dna) template. this phenomenon is involved in gene regulation mechanisms and in the development of diverse diseases. the bacteriophage λ n protein reduces transcriptional slippage within actively growing cells and in vitro. n appears to stabilize the rna/dna hybrid, particularly at the 5' end, preventing loss of register betw ...201424711367
the structures of the cuta1 proteins from thermus thermophilus and pyrococcus horikoshii: characterization of metal-binding sites and metal-induced assembly.cuta1 (copper tolerance a1) is a widespread cytoplasmic protein found in archaea, bacteria, plants and animals, including humans. in escherichia coli it is implicated in divalent metal tolerance, while the mammalian cuta1 homologue has been proposed to mediate brain enzyme acetylcholinesterase activity and copper homeostasis. the x-ray structures of cuta1 from the thermophilic bacterium thermus thermophilus (ttcuta1) with and without bound na(+) at 1.7 and 1.9 å resolution, respectively, and fro ...201424699729
molecular basis for erythromycin-dependent ribosome stalling during translation of the ermbl leader peptide.in bacteria, ribosome stalling during translation of ermbl leader peptide occurs in the presence of the antibiotic erythromycin and leads to induction of expression of the downstream macrolide resistance methyltransferase ermb. the lack of structures of drug-dependent stalled ribosome complexes (srcs) has limited our mechanistic understanding of this regulatory process. here we present a cryo-electron microscopy structure of the erythromycin-dependent ermbl-src. the structure reveals that the an ...201424662426
the lyr protein subunit nb4m/ndufa6 of mitochondrial complex i anchors an acyl carrier protein and is essential for catalytic activity.mitochondrial complex i is the largest and most complicated enzyme of the oxidative phosphorylation system. it comprises a number of so-called accessory subunits of largely unknown structure and function. here we studied subunit nb4m [ndufa6, lyr motif containing protein 6 (lyrm6)], a member of the lyrm family of proteins. chromosomal deletion of the corresponding gene in the yeast yarrowia lipolytica caused concomitant loss of the mitochondrial acyl carrier protein subunit acpm1 from the enzyme ...201424706851
capturing the bacterial holo-complex. 201424707040
moyamoya disease-associated protein mysterin/rnf213 is a novel aaa+ atpase, which dynamically changes its oligomeric state.moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. we recently identified mysterin/rnf213 as its first susceptibility gene, which encodes a 591-kda protein containing enzymatically active p-loop atpase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. here we demonstrate that mysterin further contains two tandem aaa+ atpase modules and forms huge ring-shaped oligom ...201424658080
mycobacterium tuberculosis phosphoenolpyruvate carboxykinase is regulated by redox mechanisms and interaction with thioredoxin.tuberculosis remains a major health concern worldwide. eradication of its causative agent, the bacterial pathogen mycobacterium tuberculosis, is particularly challenging due to a vast reservoir of latent carriers of the disease. despite the misleading terminology of a so-called dormant state associated with latent infections, the bacteria have to maintain basic metabolic activities. hypoxic conditions have been widely used as an in vitro system to study this dormancy. such studies identified a r ...201424659783
trans-translation exposed: understanding the structures and functions of tmrna-smpb.ribosome stalling is a serious issue for cell survival. in bacteria, the primary rescue system is trans-translation, performed by tmrna and its protein partner small protein b (smpb). since its discovery almost 20 years ago, biochemical, genetic, and structural studies have paved the way to a better understanding of how this sophisticated process takes place at the cellular and molecular levels. here we describe the molecular details of trans-translation, with special mention of recent cryo-elec ...201424711807
cation diffusion facilitators transport initiation and regulation is mediated by cation induced conformational changes of the cytoplasmic domain.cation diffusion facilitators (cdf) are part of a highly conserved protein family that maintains cellular divalent cation homeostasis in all domains of life. cdf's were shown to be involved in several human diseases, such as type-ii diabetes and neurodegenerative diseases. in this work, we employed a multi-disciplinary approach to study the activation mechanism of the cdf protein family. for this we used mamm, one of the main ion transporters of magnetosomes--bacterial organelles that enable mag ...201424658343
an in silico approach for characterization of an aminoglycoside antibiotic-resistant methyltransferase protein from pyrococcus furiosus (dsm 3638).pyrococcus furiosus is a hyperthermophilic archaea. a hypothetical protein of this archaea, pf0847, was selected for computational analysis. basic local alignment search tool and multiple sequence alignment (msa) tool were employed to search for related proteins. both the secondary and tertiary structure prediction were obtained for further analysis. three-dimensional model was assessed by procheck and qmean6 programs. to get insights about the physical and functional associations of the protein ...201424683305
nature and biosynthesis of galacto-oligosaccharides related to oligosaccharides in human breast milk.human milk oligosaccharides (hmo) are prominent among the functional components of human breast milk. while hmo have potential applications in both infants and adults, this potential is limited by the difficulties in manufacturing these complex structures. consequently, functional alternatives such as galacto-oligosaccharides are under investigation, and nowadays, infant formulae are supplemented with galacto-oligosaccharides to mimic the biological effects of hmo. recently, approaches toward th ...201424571717
secondary structure preferences of mn (2+) binding sites in bacterial proteins.3d structures of proteins with coordinated mn(2+) ions from bacteria with low, average, and high genomic gc-content have been analyzed (149 pdb files were used). major mn(2+) binders are aspartic acid (6.82% of asp residues), histidine (14.76% of his residues), and glutamic acid (3.51% of glu residues). we found out that the motif of secondary structure "beta strand-major binder-random coil" is overrepresented around all the three major mn(2+) binders. that motif may be followed by either alpha ...201424778647
rna helicase proteins as chaperones and remodelers.superfamily 2 helicase proteins are ubiquitous in rna biology and have an extraordinarily broad set of functional roles. central among these roles are the promotion of rearrangements of structured rnas and the remodeling of ribonucleoprotein complexes (rnps), allowing formation of native rna structure or progression through a functional cycle of structures. although all superfamily 2 helicases share a conserved helicase core, they are divided evolutionarily into several families, and it is princ ...201424635478
pyrrolysyl-trna synthetase: an ordinary enzyme but an outstanding genetic code expansion tool.the genetic incorporation of the 22nd proteinogenic amino acid, pyrrolysine (pyl) at amber codon is achieved by the action of pyrrolysyl-trna synthetase (pylrs) together with its cognate trna(pyl). unlike most aminoacyl-trna synthetases, pylrs displays high substrate side chain promiscuity, low selectivity toward its substrate α-amine, and low selectivity toward the anticodon of trna(pyl). these unique but ordinary features of pylrs as an aminoacyl-trna synthetase allow the pyl incorporation mac ...201424631543
evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease h active site.ribonuclease h1 (rnase h) enzymes are well-conserved endonucleases that are present in all domains of life and are particularly important in the life cycle of retroviruses as domains within reverse transcriptase. despite extensive study, especially of the e. coli homolog, the interaction of the highly negatively charged active site with catalytically required magnesium ions remains poorly understood. in this work, we describe molecular dynamics simulations of the e. coli homolog in complex with ...201425075292
a novel approach to simulate a charge transfer in dna repair by an anacystis nidulans photolyase.an anacystis nidulans photolyase enzyme containing two chromophore cofactors was simulated for a photoreaction dna repairing process via molecular dynamics (md) method. a novel approach has been introduced for the electron transfer between the fad (flavin adenine dinucleotide; flavin) molecule and cpd (cyclobutane pyrimidine dimer). this approach involves four simulation stages with different charges for the fad and cpd fragments and a role of a charged state of the active cofactor was qualified ...201424772194
automated particle picking for low-contrast macromolecules in cryo-electron microscopy.cryo-electron microscopy is an increasingly popular tool for studying the structure and dynamics of biological macromolecules at high resolution. a crucial step in automating single-particle reconstruction of a biological sample is the selection of particle images from a micrograph. we present a novel algorithm for selecting particle images in low-contrast conditions; it proves more effective than the human eye on close-to-focus micrographs, yielding improved or comparable resolution in reconstr ...201424607413
cbr antimicrobials alter coupling between the bridge helix and the β subunit in rna polymerase.bacterial rna polymerase (rnap) is a validated target for antibacterial drugs. cbr703 series antimicrobials allosterically inhibit transcription by binding to a conserved α helix (β' bridge helix, bh) that interconnects the two largest rnap subunits. here we show that disruption of the bh-β subunit contacts by amino-acid substitutions invariably results in accelerated catalysis, slowed-down forward translocation and insensitivity to regulatory pauses. cbr703 partially reverses these effects in c ...201424598909
adenylyl cyclase-associated protein 1 is a receptor for human resistin and mediates inflammatory actions of human monocytes.human resistin is a cytokine that induces low-grade inflammation by stimulating monocytes. resistin-mediated chronic inflammation can lead to obesity, atherosclerosis, and other cardiometabolic diseases. nevertheless, the receptor for human resistin has not been clarified. here, we identified adenylyl cyclase-associated protein 1 (cap1) as a functional receptor for human resistin and clarified its intracellular signaling pathway to modulate inflammatory action of monocytes. we found that human r ...201424606903
structural insights into dna repair by rnase t--an exonuclease processing 3' end of structured dna in repair pathways.dna repair mechanisms are essential for preservation of genome integrity. however, it is not clear how dna are selected and processed at broken ends by exonucleases during repair pathways. here we show that the dnaq-like exonuclease rnase t is critical for escherichia coli resistance to various dna-damaging agents and uv radiation. rnase t specifically trims the 3' end of structured dna, including bulge, bubble, and y-structured dna, and it can work with endonuclease v to restore the deaminated ...201424594808
timmdc1/c3orf1 functions as a membrane-embedded mitochondrial complex i assembly factor through association with the mcia complex.complex i (ci) of the electron transport chain, a large membrane-embedded nadh dehydrogenase, couples electron transfer to the release of protons into the mitochondrial inner membrane space to promote atp production through atp synthase. in addition to being a central conduit for atp production, ci activity has been linked to neurodegenerative disorders, including parkinson's disease. ci is built in a stepwise fashion through the actions of several assembly factors. we employed interaction prote ...201424344204
genomics of kpc-producing klebsiella pneumoniae sequence type 512 clone highlights the role of ramr and ribosomal s10 protein mutations in conferring tigecycline resistance.full genome sequences were determined for five klebsiella pneumoniae strains belonging to the sequence type 512 (st512) clone, producing kpc-3. three strains were resistant to tigecycline, one showed an intermediate phenotype, and one was susceptible. comparative analysis performed using the genome of the susceptible strain as a reference sequence identified genetic differences possibly associated with resistance to tigecycline. results demonstrated that mutations in the ramr gene occurred in tw ...201424379204
an archaeal glutamate decarboxylase homolog functions as an aspartate decarboxylase and is involved in β-alanine and coenzyme a biosynthesis.β-alanine is a precursor for coenzyme a (coa) biosynthesis and is a substrate for the bacterial/eukaryotic pantothenate synthetase and archaeal phosphopantothenate synthetase. β-alanine is synthesized through various enzymes/pathways in bacteria and eukaryotes, including the direct decarboxylation of asp by aspartate 1-decarboxylase (adc), the degradation of pyrimidine, or the oxidation of polyamines. however, in most archaea, homologs of these enzymes are not present; thus, the mechanisms of β- ...201424415726
functional characterization of osmotically inducible protein c (mg_427) from mycoplasma genitalium.mycoplasma genitalium is the smallest self-replicating bacterium and an important human pathogen responsible for a range of urogenital infections and pathologies. due to its limited genome size, many genes conserved in other bacteria are missing in m. genitalium. genes encoding catalase and superoxide dismutase are absent, and how this pathogen overcomes oxidative stress remains poorly understood. in this study, we characterized mg_427, a homolog of the conserved osmc, which encodes hydroperoxid ...201424363346
trna anticodon shifts in eukaryotic genomes.embedded in the sequence of each transfer rna are elements that promote specific interactions with its cognate aminoacyl trna-synthetase. although many such "identity elements" are known, their detection is difficult since they rely on unique structural signatures and the combinatorial action of multiple elements spread throughout the trna molecule. since the anticodon is often a major identity determinant itself, it is possible to switch between certain trna functional types by means of anticod ...201424442610
structure and mechanism of soybean atp sulfurylase and the committed step in plant sulfur assimilation.enzymes of the sulfur assimilation pathway are potential targets for improving nutrient content and environmental stress responses in plants. the committed step in this pathway is catalyzed by atp sulfurylase, which synthesizes adenosine 5'-phosphosulfate (aps) from sulfate and atp. to better understand the molecular basis of this energetically unfavorable reaction, the x-ray crystal structure of atp sulfurylase isoform 1 from soybean (glycine max atp sulfurylase) in complex with aps was determi ...201424584934
halorhabdus tiamatea: proteogenomics and glycosidase activity measurements identify the first cultivated euryarchaeon from a deep-sea anoxic brine lake as potential polysaccharide degrader.euryarchaea from the genus halorhabdus have been found in hypersaline habitats worldwide, yet are represented by only two isolates: halorhabdus utahensis ax-2(t) from the shallow great salt lake of utah, and halorhabdus tiamatea sarl4b(t) from the shaban deep-sea hypersaline anoxic lake (dhal) in the red sea. we sequenced the h. tiamatea genome to elucidate its niche adaptations. among sequenced archaea, h. tiamatea features the highest number of glycoside hydrolases, the majority of which were ...201424428220
transcription elongation. heterogeneous tracking of rna polymerase and its biological implications.regulation of transcription elongation via pausing of rna polymerase has multiple physiological roles. the pausing mechanism depends on the sequence heterogeneity of the dna being transcribed, as well as on certain interactions of polymerase with specific dna sequences. in order to describe the mechanism of regulation, we introduce the concept of heterogeneity into the previously proposed alternative models of elongation, power stroke and brownian ratchet. we also discuss molecular origins and p ...201425764114
insights into the glycosylase search for damage from single-molecule fluorescence microscopy.the first step of base excision repair utilizes glycosylase enzymes to find damage within a genome. a persistent question in the field of dna repair is how glycosylases interact with dna to specifically find and excise target damaged bases with high efficiency and specificity. ensemble studies have indicated that glycosylase enzymes rely upon both sliding and distributive modes of search, but ensemble methods are limited in their ability to directly observe these modes. here we review insights i ...201424560296
high-affinity gold nanoparticle pin to label and localize histidine-tagged protein in macromolecular assemblies.there is significant demand for experimental approaches to aid protein localization in electron microscopy micrographs and ultimately in three-dimensional reconstructions of macromolecular assemblies. we report preparation and use of a reagent consisting of tris-nitrilotriacetic acid (tris-nta) conjugated with a monofunctional gold nanoparticle ((aunp)tris-nta) for site-specific, non-covalent labeling of protein termini fused to a histidine-tag (his-tag). multivalent binding of tris-nta to a his ...201424560806
mechanism of trans-translation revealed by in vitro studies.tmrna is a bacterial small rna having a structure resembling the upper half of trna and its 3' end accepts alanine followed by binding to ef-tu like trna. instead of lacking a lower half of the cloverleaf structure including the anticodon, tmrna has a short coding sequence for tag-peptide that serves as a target of cellular proteases. an elaborate coordination of two functions as trna and mrna facilitates an irregular translation termed trans-translation: a single polypeptide is synthesized from ...201424600445
tetartohedral twinning in idi-2 from thermus thermophilus: crystallization under anaerobic conditions.type-2 isopentenyl diphosphate isomerase (idi-2) is a key flavoprotein involved in the biosynthesis of isoprenoids. since fully reduced flavin mononucleotide (fmnh2) is needed for activity, it was decided to crystallize the enzyme under anaerobic conditions in order to understand how this reduced cofactor binds within the active site and interacts with the substrate isopentenyl diphosphate (ipp). in this study, the protein was expressed and purified under aerobic conditions and then reduced and ...201424598924
paclitaxel induces apoptosis in breast cancer cells through different calcium--regulating mechanisms depending on external calcium conditions.previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. furthermore, the actions of paclitaxel attenuated bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. to better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and/or ...201424549172
dna-guided dna interference by a prokaryotic argonaute.rna interference is widely distributed in eukaryotes and has a variety of functions, including antiviral defence and gene regulation. all rna interference pathways use small single-stranded rna (ssrna) molecules that guide proteins of the argonaute (ago) family to complementary ssrna targets: rna-guided rna interference. the role of prokaryotic ago variants has remained elusive, although bioinformatics analysis has suggested their involvement in host defence. here we demonstrate that ago of the ...201424531762
ion mobility-mass spectrometry of a rotary atpase reveals atp-induced reduction in conformational flexibility.rotary atpases play fundamental roles in energy conversion as their catalytic rotation is associated with interdomain fluctuations and heterogeneity of conformational states. using ion mobility mass spectrometry we compared the conformational dynamics of the intact atpase from thermus thermophilus with those of its membrane and soluble subcomplexes. our results define regions with enhanced flexibility assigned to distinct subunits within the overall assembly. to provide a structural context for ...201424557135
the k-junction motif in rna structure.the k-junction is a structural motif in rna comprising a three-way helical junction based upon kink turn (k-turn) architecture. a computer program written to examine relative helical orientation identified the three-way junction of the arabidopsis tpp riboswitch as an elaborated k-turn. the escherichia coli tpp riboswitch contains a related k-junction, and analysis of >11 000 sequences shows that the structure is common to these riboswitches. the k-junction exhibits all the key features of an n1 ...201424531930
chlorite dismutases - a heme enzyme family for use in bioremediation and generation of molecular oxygen.chlorite is a serious environmental concern, as rising concentrations of this harmful anthropogenic compound have been detected in groundwater, drinking water, and soil. chlorite dismutases (clds) are therefore important molecules in bioremediation as clds catalyze the degradation of chlorite to chloride and molecular oxygen. clds are heme b-containing oxidoreductases present in numerous bacterial and archaeal phyla. this review presents the phylogeny of functional clds and cld-like proteins, an ...201424519858
using ¹⁵n-ammonium to characterise and map potassium binding sites in proteins by nmr spectroscopy.a variety of enzymes are activated by the binding of potassium ions. the potassium binding sites of these enzymes are very specific, but ammonium ions can often replace potassium ions in vitro because of their similar ionic radii. in these cases, ammonium can be used as a proxy for potassium to characterise potassium binding sites in enzymes: the (1) h,(15) n spin-pair of enzyme-bound (15) nh4 (+) can be probed by (15) n-edited heteronuclear nmr experiments. here, we demonstrate the use of nmr s ...201424520048
the putative trna 2-thiouridine synthetase ncs6 is an essential sulfur carrier in methanococcus maripaludis.thiolation of carbon-2 of uridine located in the first position of the anticodons of trnauug(gln), trnauuc(glu), and trnauuu(lys) is a conserved rna modification event requiring the 2-thiouridine synthetase ncs6/ctu1 in archaea and eukaryotes. ncs6/ctu1 activates uridine by adenylation, but its role in sulfur transfer is unclear. here we show that mmp1356, the ncs6/ctu1 homolog in the archaeon methanococcus maripaludis, forms a persulfide enzyme adduct with an active site cysteine; this suggests ...201424530533
structural basis and target-specific modulation of adp sensing by the synechococcus elongatus pii signaling protein.pii signaling proteins comprise one of the most versatile signaling devices in nature and have a highly conserved structure. in cyanobacteria, pipx and n-acetyl-l-glutamate kinase are receptors of pii signaling, and these interactions are modulated by adp, atp, and 2-oxoglutarate. these effector molecules bind interdependently to three anti-cooperative binding sites on the trimeric pii protein and thereby affect its structure. here we used the pii protein from synechococcus elongatus pcc 7942 to ...201424519945
a new system for naming ribosomal proteins.a system for naming ribosomal proteins is described that the authors intend to use in the future. they urge others to adopt it. the objective is to eliminate the confusion caused by the assignment of identical names to ribosomal proteins from different species that are unrelated in structure and function. in the system proposed here, homologous ribosomal proteins are assigned the same name, regardless of species. it is designed so that new names are similar enough to old names to be easily recog ...201424524803
inhibition of the 4fe-4s proteins ispg and isph: an epr, endor and hyscore investigation.ispg and isph are proteins that are involved in isoprenoid biosynthesis in most bacteria as well as in malaria parasites and are important drug targets. they contain cubane-type 4fe-4s clusters that are involved in unusual 2h(+)/2e(-) reductions. here, we report the results of electron paramagnetic resonance spectroscopic investigations of the binding of amino- and thiolo-hmbpp (hmbpp=e-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate) isph substrate-analog inhibitors to both proteins, as well as the ...201424999381
fast proton-coupled electron transfer observed for a high-fidelity structural and functional [2fe-2s] rieske model.rieske cofactors have a [2fe-2s] cluster with unique {his2cys2} ligation and distinct fe subsites. the histidine ligands are functionally relevant, since they allow for coupling of electron and proton transfer (pcet) during quinol oxidation in respiratory and photosynthetic et chains. here we present the highest fidelity synthetic analogue for the rieske [2fe-2s] cluster reported so far. this synthetic analogue 5(x-) emulates the heteroleptic {his2cys2} ligation of the [2fe-2s] core, and it also ...201424506804
structural studies of yeast δ(1)-pyrroline-5-carboxylate dehydrogenase (aldh4a1): active site flexibility and oligomeric state.the proline catabolic enzyme δ(1)-pyrroline-5-carboxylate dehydrogenase (aldh4a1) catalyzes the nad(+)-dependent oxidation of γ-glutamate semialdehyde to l-glutamate. in saccharomyces cerevisiae, aldh4a1 is encoded by the put2 gene and known as put2p. here we report the steady-state kinetic parameters of the purified recombinant enzyme, two crystal structures of put2p, and the determination of the oligomeric state and quaternary structure from small-angle x-ray scattering and sedimentation veloc ...201424502590
in vitro assembly and activity of an archaeal crispr-cas type i-a cascade interference complex.clustered regularly interspaced short palindromic repeats (crispr)-crispr-associated (cas) systems of type i use a cas ribonucleoprotein complex for antiviral defense (cascade) to mediate the targeting and degradation of foreign dna. to address molecular features of the archaeal type i-a cascade interference mechanism, we established the in vitro assembly of the thermoproteus tenax cascade from six recombinant cas proteins, synthetic crispr rnas (crrnas) and target dna fragments. rna-seq analyse ...201424500198
coexistence of bacterial leucyl-trna synthetases with archaeal trna binding domains that distinguish trna(leu) in the archaeal mode.leucyl-trna (transfer rna) synthetase (leurs) is a multi-domain enzyme, which is divided into bacterial and archaeal/eukaryotic types. in general, one specific leurs, the domains of which are of the same type, exists in a single cell compartment. however, some species, such as the haloalkaliphile natrialba magadii, encode two cytoplasmic leurss, nmleurs1 and nmleurs2, which are the first examples of naturally occurring chimeric enzymes with different domains of bacterial and archaeal types. furt ...201424500203
secondary structures of rrnas from all three domains of life.accurate secondary structures are important for understanding ribosomes, which are extremely large and highly complex. using 3d structures of ribosomes as input, we have revised and corrected traditional secondary (2°) structures of rrnas. we identify helices by specific geometric and molecular interaction criteria, not by co-variation. the structural approach allows us to incorporate non-canonical base pairs on parity with watson-crick base pairs. the resulting rrna 2° structures are up-to-date ...201424505437
a cylindrical specimen holder for electron cryo-tomography.the use of slab-like flat specimens for electron cryo-tomography restricts the range of viewing angles that can be used. this leads to the "missing wedge" problem, which causes artefacts and anisotropic resolution in reconstructed tomograms. cylindrical specimens provide a way to eliminate the problem, since they allow imaging from a full range of viewing angles around the tilt axis. such specimens have been used before for tomography of radiation-insensitive samples at room temperature, but nev ...201424275523
an unusual mechanism for ef-tu activation during tmrna-mediated ribosome rescue.in bacteria, ribosomes stalled on truncated mrnas are rescued by transfer-messenger rna (tmrna) and its protein partner smpb. acting like trna, the aminoacyl-tmrna/smpb complex is delivered to the ribosomal a site by ef-tu and accepts the transfer of the nascent polypeptide. although smpb binding within the decoding center is clearly critical for licensing tmrna entry into the ribosome, it is not known how activation of ef-tu occurs in the absence of a codon-anticodon interaction. a recent cryst ...201424345396
bioorganometallic chemistry with ispg and isph: structure, function, and inhibition of the [fe(4)s(4)] proteins involved in isoprenoid biosynthesis.enzymes of the methylerythritol phosphate pathway of isoprenoid biosynthesis are attractive anti-infective drug targets. the last two enzymes of this pathway, ispg and isph, are [fe4 s4 ] proteins that are not produced by humans and catalyze 2 h(+) / 2 e(-) reductions with novel mechanisms. in this review, we summarize recent advances in structural, mechanistic, and inhibitory studies of these two enzymes. in particular, mechanistic proposals involving bioorganometallic intermediates are present ...201424481599
elements in nucleotide sensing and hydrolysis of the aaa+ disaggregation machine clpb: a structure-based mechanistic dissection of a molecular motor.atpases of the aaa+ superfamily are large oligomeric molecular machines that remodel their substrates by converting the energy from atp hydrolysis into mechanical force. this study focuses on the molecular chaperone clpb, the bacterial homologue of hsp104, which reactivates aggregated proteins under cellular stress conditions. based on high-resolution crystal structures in different nucleotide states, mutational analysis and nucleotide-binding kinetics experiments, the atpase cycle of the c-term ...201424531492
crystal structure of e. coli arginyl-trna synthetase and ligand binding studies revealed key residues in arginine recognition.the arginyl-trna synthetase (argrs) catalyzes the esterification reaction between l-arginine and its cognate trna(arg). previously reported structures of argrs shed considerable light on the trna recognition mechanism, while the aspect of amino acid binding in argrs remains largely unexplored. here we report the first crystal structure of e. coli argrs (eargrs) complexed with l-arginine, and a series of mutational studies using isothermal titration calorimetry (itc). combined with previously rep ...201424474195
global patterns of protein domain gain and loss in superkingdoms.domains are modules within proteins that can fold and function independently and are evolutionarily conserved. here we compared the usage and distribution of protein domain families in the free-living proteomes of archaea, bacteria and eukarya and reconstructed species phylogenies while tracing the history of domain emergence and loss in proteomes. we show that both gains and losses of domains occurred frequently during proteome evolution. the rate of domain discovery increased approximately lin ...201424499935
discovery and characterization of ionic liquid-tolerant thermophilic cellulases from a switchgrass-adapted microbial community.the development of advanced biofuels from lignocellulosic biomass will require the use of both efficient pretreatment methods and new biomass-deconstructing enzyme cocktails to generate sugars from lignocellulosic substrates. certain ionic liquids (ils) have emerged as a promising class of compounds for biomass pretreatment and have been demonstrated to reduce the recalcitrance of biomass for enzymatic hydrolysis. however, current commercial cellulase cocktails are strongly inhibited by most of ...201424479406
binding of copper and silver to single-site variants of peptidylglycine monooxygenase reveals the structure and chemistry of the individual metal centers.peptidylglycine monooxygenase (phm) catalyzes the final step in the biosynthesis of amidated peptides that serve as important signaling molecules in numerous endocrine pathways. the catalytic mechanism has attracted much attention because of a number of unique attributes, including the presence of a pair of uncoupled copper centers separated by 11 å (termed cuh and cum), an unusual cu(i)smet interaction at the oxygen binding m-site, and the postulated cu(ii)-superoxo intermediate. understanding ...201424471980
the omega subunit of the rna polymerase core directs transcription efficiency in cyanobacteria.the eubacterial rna polymerase core, a transcription machinery performing dna-dependent rna polymerization, consists of two α subunits and β, β' and ω subunits. an additional σ subunit is recruited for promoter recognition and transcription initiation. cyanobacteria, a group of eubacteria characterized by oxygenic photosynthesis, have a unique composition of the rna polymerase (rnap) core due to splitting of the β' subunit to n-terminal γ and c-terminal β' subunits. the physiological roles of th ...201424476911
a bacteriophage transcription regulator inhibits bacterial transcription initiation by σ-factor displacement.bacteriophages (phages) appropriate essential processes of bacterial hosts to benefit their own development. the multisubunit bacterial rna polymerase (rnap) enzyme, which catalyses dna transcription, is targeted by phage-encoded transcription regulators that selectively modulate its activity. here, we describe the structural and mechanistic basis for the inhibition of bacterial rnap by the transcription regulator p7 encoded by xanthomonas oryzae phage xp10. we reveal that p7 uses a two-step mec ...201424482445
4'-o-substitutions determine selectivity of aminoglycoside antibiotics.clinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. here we present a series of 4',6'-o-acetal and 4'-o-ether modifications on glucopyranosyl ring i of aminoglycosides. chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact ...201424473108
a complex of cas proteins 5, 6, and 7 is required for the biogenesis and stability of clustered regularly interspaced short palindromic repeats (crispr)-derived rnas (crrnas) in haloferax volcanii.the clustered regularly interspaced short palindromic repeats/crispr-associated (crispr-cas) system is a prokaryotic defense mechanism against foreign genetic elements. a plethora of crispr-cas versions exist, with more than 40 different cas protein families and several different molecular approaches to fight the invading dna. one of the key players in the system is the crispr-derived rna (crrna), which directs the invader-degrading cas protein complex to the invader. the crispr-cas types i and ...201424459147
characterization of cleavage intermediate and star sites of rm.tth111ii.tth111ii is a thermostable type iigs restriction enzyme that recognizes dna sites caarca (r = a or g) and cleaves downstream at n11/n9. here, the tth111iirm gene was cloned and expressed in e. coli, and tth111ii was purified. the purified enzyme contains internally-bound s-adenosylmethionine (sam). when the internal sam was removed, the endonuclease activity was stimulated by adding sam or its analog sinefungin. the cleavage intermediate is mostly top-strand nicked dna on a single-site plasmid. ...201424452415
subunit positioning and stator filament stiffness in regulation and power transmission in the v1 motor of the manduca sexta v-atpase.the vacuolar h(+)-atpase (v-atpase) is an atp-driven proton pump essential to the function of eukaryotic cells. its cytoplasmic v1 domain is an atpase, normally coupled to membrane-bound proton pump vo via a rotary mechanism. how these asymmetric motors are coupled remains poorly understood. low energy status can trigger release of v1 from the membrane and curtail atp hydrolysis. to investigate the molecular basis for these processes, we have carried out cryo-electron microscopy three-dimensiona ...201424075871
folding a stable rna pseudoknot through rearrangement of two hairpin structures.folding messenger rna into specific structures is a common regulatory mechanism involved in translation. in escherichia coli, the operator of the rpso gene transcript folds into a pseudoknot or double-hairpin conformation. s15, the gene product, binds only to the pseudoknot, thereby repressing its own synthesis when it is present in excess in the cell. the two rna conformations have been proposed to exist in equilibrium. however, it remained unclear how structural changes can be achieved between ...201424459133
dynamic protein ligand interactions--insights from ms.proteins undergo dynamic interactions with carbohydrates, lipids and nucleotides to form catalytic cores, fine-tuned for different cellular actions. the study of dynamic interactions between proteins and their cognate ligands is therefore fundamental to the understanding of biological systems. during the last two decades ms, and its associated techniques, has become accepted as a method for the study of protein-ligand interactions, not only for covalent complexes, where the use of ms is well est ...201424393119
distinct functions of the rna polymerase σ subunit region 3.2 in rna priming and promoter escape.the σ subunit of bacterial rna polymerase (rnap) has been implicated in all steps of transcription initiation, including promoter recognition and opening, priming of rna synthesis, abortive initiation and promoter escape. the post-promoter-recognition σ functions were proposed to depend on its conserved region σ3.2 that directly contacts promoter dna immediately upstream of the rnap active centre and occupies the rna exit path. analysis of the transcription effects of substitutions and deletions ...201424452800
a highly divergent archaeo-eukaryotic primase from the thermococcus nautilus plasmid, ptn2.we report the characterization of a dna primase/polymerase protein (polptn2) encoded by the ptn2 plasmid from thermococcus nautilus. sequence analysis revealed that this protein corresponds to a fusion between an n-terminal domain homologous to the small catalytic subunit pris of heterodimeric archaeal and eukaryotic primases (aep) and a c-terminal domain related to their large regulatory subunit pril. this unique domain configuration is not found in other virus- and plasmid-encoded primases in ...201424445805
structural and functional analyses of a sterol carrier protein in spodoptera litura.in insects, cholesterol is one of the membrane components in cells and a precursor of ecdysteroid biosynthesis. because insects lack two key enzymes, squalene synthase and lanosterol synthase, in the cholesterol biosynthesis pathway, they cannot autonomously synthesize cholesterol de novo from simple compounds and therefore have to obtain sterols from their diet. sterol carrier protein (scp) is a cholesterol-binding protein responsible for cholesterol absorption and transport.201424454688
context of action of proline dehydrogenase (prodh) in the hypersensitive response of arabidopsis.proline (pro) dehydrogenase (prodh) potentiates the oxidative burst and cell death of the plant hypersensitive response (hr) by mechanisms not yet elucidated. prodh converts pro into ∆1 pyrroline-5-carboxylate (p5c) and can act together with p5c dehydrogenase (p5cdh) to produce glu, or with p5c reductase (p5cr) to regenerate pro and thus stimulate the pro/p5c cycle. to better understand the effects of prodh in hr, we studied the enzyme at three stages of the defense response differing in their r ...201424410747
the isolated carboxy-terminal domain of human mitochondrial leucyl-trna synthetase rescues the pathological phenotype of mitochondrial trna mutations in human cells.mitochondrial (mt) diseases are multisystem disorders due to mutations in nuclear or mtdna genes. among the latter, more than 50% are located in transfer rna (trna) genes and are responsible for a wide range of syndromes, for which no effective treatment is available at present. we show that three human mt aminoacyl-trna syntethases, namely leucyl-, valyl-, and isoleucyl-trna synthetase are able to improve both viability and bioenergetic proficiency of human transmitochondrial cybrid cells carry ...201424413190
crystal structures of ispf from plasmodium falciparum and burkholderia cenocepacia: comparisons inform antimicrobial drug target assessment.2c-methyl-d-erythritol-2,4-cyclodiphosphate synthase (ispf) catalyzes the conversion of 4-diphosphocytidyl-2c-methyl-d-erythritol-2-phosphate to 2c-methyl-d-erythritol-2,4-cyclodiphosphate and cytidine monophosphate in production of isoprenoid-precursors via the methylerythritol phosphate biosynthetic pathway. ispf is found in the protozoan plasmodium falciparum, a parasite that causes cerebral malaria, as well as in many gram-negative bacteria such as burkholderia cenocepacia. ispf represents a ...201424410837
mlh1-mlh3, a meiotic crossover and dna mismatch repair factor, is a msh2-msh3-stimulated endonuclease.crossing over between homologous chromosomes is initiated in meiotic prophase in most sexually reproducing organisms by the appearance of programmed double strand breaks throughout the genome. in saccharomyces cerevisiae the double-strand breaks are resected to form three prime single-strand tails that primarily invade complementary sequences in unbroken homologs. these invasion intermediates are converted into double holliday junctions and then resolved into crossovers that facilitate homolog s ...201424403070
Refresh
firstprev
...41424344454647484950...
nextlast
Displaying items 4601 - 4700 of 5451