Publications

a high-throughput assay for the comprehensive profiling of dna ligase fidelity.	dna ligases have broad application in molecular biology, from traditional cloning methods to modern synthetic biology and molecular diagnostics protocols. ligation-based detection of polynucleotide sequences can be achieved by the ligation of probe oligonucleotides when annealed to a complementary target sequence. in order to achieve a high sensitivity and low background, the ligase must efficiently join correctly base-paired substrates, while discriminating against the ligation of substrates co ...	2015	26365241
mismatch repair.	highly conserved muts homologs (msh) and mutl homologs (mlh/pms) are the fundamental components of mismatch repair (mmr). after decades of debate, it appears clear that the msh proteins initiate mmr by recognizing a mismatch and forming multiple extremely stable atp-bound sliding clamps that diffuse without hydrolysis along the adjacent dna. the function(s) of mlh/pms proteins is less clear, although they too bind atp and are targeted to mmr by msh sliding clamps. structural analysis combined wi ...	2015	26354434
binuclear cu(a) formation in biosynthetic models of cu(a) in azurin proceeds via a novel cu(cys)2his mononuclear copper intermediate.	cu(a) is a binuclear electron transfer (et) center found in cytochrome c oxidases (ccos), nitrous oxide reductases (n₂ors), and nitric oxide reductase (nor). in these proteins, the cu(a) centers facilitate efficient et (ket > 10⁴s⁻¹) under low thermodynamic driving forces (10-90 mv). while the structure and functional properties of cu(a) are well understood, a detailed mechanism of the incorporation of copper into the protein and the identity of the intermediates formed during the cu(a) maturati ...	2015	26352296
loop recognition and copper-mediated disulfide reduction underpin metal site assembly of cua in human cytochrome oxidase.	maturation of cytochrome oxidases is a complex process requiring assembly of several subunits and adequate uptake of the metal cofactors. two orthologous sco proteins (sco1 and sco2) are essential for the correct assembly of the dicopper cua site in the human oxidase, but their function is not fully understood. here, we report an in vitro biochemical study that shows that sco1 is a metallochaperone that selectively transfers cu(i) ions based on loop recognition, whereas sco2 is a copper-dependen ...	2015	26351686
card uses a minor groove wedge mechanism to stabilize the rna polymerase open promoter complex.	a key point to regulate gene expression is at transcription initiation, and activators play a major role. card, an essential activator in mycobacterium tuberculosis, is found in many bacteria, including thermus species, but absent in escherichia coli. to delineate the molecular mechanism of card, we determined crystal structures of thermus transcription initiation complexes containing card. the structures show card interacts with the unique dna topology presented by the upstream double-stranded/ ...	2015	26349034
the presence of highly disruptive 16s rrna mutations in clinical samples indicates a wider role for mutations of the mitochondrial ribosome in human disease.	mitochondrial dna mutations are well recognized as an important cause of disease, with over two hundred variants in the protein encoding and mt-trna genes associated with human disorders. in contrast, the two genes encoding the mitochondrial rrnas (mt-rrnas) have been studied in far less detail. this is because establishing the pathogenicity of mt-rrna mutations is a major diagnostic challenge. only two disease causing mutations have been identified at these loci, both mapping to the small subun ...	2015	26349026
characterization of clinically identified mutations in ndufv1, the flavin-binding subunit of respiratory complex i, using a yeast model system.	dysfunctions in mitochondrial complex i (nadh:ubiquinone oxidoreductase) are both genetically and clinically highly diverse and a major cause of human mitochondrial diseases. the genetic determinants of individual clinical cases are increasingly being described, but how these genetic defects affect complex i on the molecular and cellular level, and have different clinical consequences in different individuals, is little understood. furthermore, without molecular-level information innocent geneti ...	2015	26345448
mechanisms of microrna turnover.	micrornas (mirnas) are 20-24 nucleotide (nt) rnas that regulate gene expression by guiding argonaute (ago) proteins to specific target rnas to cause their degradation or translational repression. the abundance of mirnas is strictly controlled at the transcriptional or post-transcriptional levels. mirna turnover is presumably a necessary means to regulate mirna levels in response to physiological, developmental, and environmental changes. mirna 3' end methylation, 3' end nucleotide addition, ago ...	2015	26342825
the landscape of intertwined associations in homooligomeric proteins.	we present an overview of the full repertoire of intertwined associations in homooligomeric proteins. this overview summarizes recent findings on the different categories of intertwined associations in known protein structures, their assembly modes, the properties of their interfaces, and their structural plasticity. furthermore, the current body of knowledge on the so-called three-dimensional domain-swapped systems is reexamined in the context of the wider landscape of intertwined homooligomers ...	2015	26340815
the use of polyoxometalates in protein crystallography - an attempt to widen a well-known bottleneck.	polyoxometalates (poms) are discrete polynuclear metal-oxo anions with a fascinating variety of structures and unique chemical and physical properties. their application in various fields is well covered in the literature, however little information about their usage in protein crystallization is available. this review summarizes the impact of the vast class of poms on the formation of protein crystals, a well-known (frustrating) bottleneck in macromolecular crystallography, with the associated ...	2015	26339074
structures of archaeal dna segregation machinery reveal bacterial and eukaryotic linkages.	although recent studies have provided a wealth of information about archaeal biology, nothing is known about the molecular basis of dna segregation in these organisms. here, we unveil the machinery and assembly mechanism of the archaeal sulfolobus pnob8 partition system. this system uses three proteins: para; an atypical parb adaptor; and a centromere-binding component, aspa. aspa utilizes a spreading mechanism to create a dna superhelix onto which parb assembles. this supercomplex links to the ...	2015	26339031
essentiality of threonylcarbamoyladenosine (t(6)a), a universal trna modification, in bacteria.	threonylcarbamoyladenosine (t(6)a) is a modified nucleoside universally conserved in trnas in all three kingdoms of life. the recently discovered genes for t(6)a synthesis, including tsac and tsad, are essential in model prokaryotes but not essential in yeast. these genes had been identified as antibacterial targets even before their functions were known. however, the molecular basis for this prokaryotic-specific essentiality has remained a mystery. here, we show that t(6)a is a strong positive ...	2015	26337258
stay wet, stay stable? how internal water helps the stability of thermophilic proteins.	we present a systematic computational investigation of the internal hydration of a set of homologous proteins of different stability content and molecular complexities. the goal of the study is to verify whether structural water can be part of the molecular mechanisms ensuring enhanced stability in thermophilic enzymes. our free-energy calculations show that internal hydration in the thermophilic variants is generally more favorable, and that the cumulated effect of wetting multiple sites result ...	2015	26335353
toward a whole-cell model of ribosome biogenesis: kinetic modeling of ssu assembly.	central to all life is the assembly of the ribosome: a coordinated process involving the hierarchical association of ribosomal proteins to the rnas forming the small and large ribosomal subunits. the process is further complicated by effects arising from the intracellular heterogeneous environment and the location of ribosomal operons within the cell. we provide a simplified model of ribosome biogenesis in slow-growing escherichia coli. kinetic models of in vitro small-subunit reconstitution at ...	2015	26333594
redox-induced activation of the proton pump in the respiratory complex i.	complex i functions as a redox-linked proton pump in the respiratory chains of mitochondria and bacteria, driven by the reduction of quinone (q) by nadh. remarkably, the distance between the q reduction site and the most distant proton channels extends nearly 200 å. to elucidate the molecular origin of this long-range coupling, we apply a combination of large-scale molecular simulations and a site-directed mutagenesis experiment of a key residue. in hybrid quantum mechanics/molecular mechanics s ...	2015	26330610
evidence for an induced conformational change in the catalytic mechanism of homoisocitrate dehydrogenase for saccharomyces cerevisiae: characterization of the d271n mutant enzyme.	homoisocitrate dehydrogenase (hicdh) catalyzes the nad(+)-dependent oxidative decarboxylation of hic to α-ketoadipate, the fourth step in the α-aminoadipate pathway responsible for the de novo synthesis of l-lysine in fungi. a mechanism has been proposed for the enzyme that makes use of a lys-tyr pair as acid-base catalysts, with lys acting as a base to accept a proton from the α-hydroxyl of homoisocitrate, and tyr acting as an acid to protonate the c3 of the enol of α-ketoadipate in the enoliza ...	2015	26325079
ribosome hibernation facilitates tolerance of stationary-phase bacteria to aminoglycosides.	upon entry into stationary phase, bacteria dimerize 70s ribosomes into translationally inactive 100s particles by a process called ribosome hibernation. previously, we reported that the hibernation-promoting factor (hpf) of listeria monocytogenes is required for 100s particle formation and facilitates adaptation to a number of stresses. here, we demonstrate that hpf is required for the high tolerance of stationary-phase cultures to aminoglycosides but not to beta-lactam or quinolone antibiotics. ...	2015	26324267
plasmodium apicoplast gln-trnagln biosynthesis utilizes a unique gatab amidotransferase essential for erythrocytic stage parasites.	the malaria parasite plasmodium falciparum apicoplast indirect aminoacylation pathway utilizes a non-discriminating glutamyl-trna synthetase to synthesize glu-trna(gln) and a glutaminyl-trna amidotransferase to convert glu-trna(gln) to gln-trna(gln). here, we show that plasmodium falciparum and other apicomplexans possess a unique heterodimeric glutamyl-trna amidotransferase consisting of gata and gatb subunits (gatab). we localized the p. falciparum gata and gatb subunits to the apicoplast in b ...	2015	26318454
crystal structure of staphylococcus aureus cas9.	the rna-guided dna endonuclease cas9 cleaves double-stranded dna targets with a protospacer adjacent motif (pam) and complementarity to the guide rna. recently, we harnessed staphylococcus aureus cas9 (sacas9), which is significantly smaller than streptococcus pyogenes cas9 (spcas9), to facilitate efficient in vivo genome editing. here, we report the crystal structures of sacas9 in complex with a single guide rna (sgrna) and its double-stranded dna targets, containing the 5'-ttgaat-3' pam and th ...	2015	26317473
inhibition of human glut1 and glut5 by plant carbohydrate products; insights into transport specificity.	glucose transporters glut1 (transports glucose) and glut5 (transports fructose), in addition to their functions in normal metabolism, have been implicated in several diseases including cancer and diabetes. while glut1 has several inhibitors, none have been described for glut5. by transport activity assays we found two plant products, rubusoside (from rubus suavissimus) and astragalin-6-glucoside (a glycosylated derivative of astragalin, from phytolacca americana) that inhibited human glut5. thes ...	2015	26306809
a unique uracil-dna binding protein of the uracil dna glycosylase superfamily.	uracil dna glycosylases (udgs) are an important group of dna repair enzymes, which pioneer the base excision repair pathway by recognizing and excising uracil from dna. based on two short conserved sequences (motifs a and b), udgs have been classified into six families. here we report a novel udg, udgx, from mycobacterium smegmatis and other organisms. udgx specifically recognizes uracil in dna, forms a tight complex stable to sodium dodecyl sulphate, 2-mercaptoethanol, urea and heat treatment, ...	2015	26304551
functional characterization and expression analysis of rice δ(1)-pyrroline-5-carboxylate dehydrogenase provide new insight into the regulation of proline and arginine catabolism.	while intracellular proline accumulation in response to various stress conditions has been investigated in great detail, the biochemistry and physiological relevance of proline degradation in plants is much less understood. moreover, the second and last step in proline catabolism, the oxidation of δ(1)-pyrroline-5-carboxylic acid (p5c) to glutamate, is shared with arginine catabolism. little information is available to date concerning the regulatory mechanisms coordinating these two pathways. ex ...	2015	26300893
structure of ribosomal silencing factor bound to mycobacterium tuberculosis ribosome.	the ribosomal silencing factor rsfs slows cell growth by inhibiting protein synthesis during periods of diminished nutrient availability. the crystal structure of mycobacterium tuberculosis (mtb) rsfs, together with the cryo-electron microscopy (em) structure of the large subunit 50s of mtb ribosome, reveals how inhibition of protein synthesis by rsfs occurs. rsfs binds to the 50s at l14, which, when occupied, blocks the association of the small subunit 30s. although mtb rsfs is a dimer in solut ...	2015	26299947
pyranopterin coordination controls molybdenum electrochemistry in escherichia coli nitrate reductase.	we test the hypothesis that pyranopterin (ppt) coordination plays a critical role in defining molybdenum active site redox chemistry and reactivity in the mononuclear molybdoenzymes. the molybdenum atom of escherichia coli nitrate reductase a (narghi) is coordinated by two ppt-dithiolene chelates that are defined as proximal and distal based on their proximity to a [4fe-4s] cluster known as fs0. we examined variants of two sets of residues involved in ppt coordination: (i) those interacting dire ...	2015	26297003
argonaute 2: a novel rising star in cancer research.	ago2 (argonaute 2, eif2c2) is the only member in ago family with catalytic activity and of extreme importance during small rnas guided gene silencing processes. the structural investigations have provided insights into details and functional mechanisms of the four major domains within ago2. as a multifunction player, ago2 has been revealed involved in tumorgenesis through mirnas-dependent or independent ways. and nowadays, ago2 has also been more importantly found ectopically over-expressed in c ...	2015	26284139
physiological implications of arginine metabolism in plants.	nitrogen is a limiting resource for plant growth in most terrestrial habitats since large amounts of nitrogen are needed to synthesize nucleic acids and proteins. among the 21 proteinogenic amino acids, arginine has the highest nitrogen to carbon ratio, which makes it especially suitable as a storage form of organic nitrogen. synthesis in chloroplasts via ornithine is apparently the only operational pathway to provide arginine in plants, and the rate of arginine synthesis is tightly regulated by ...	2015	26284079
parametrization of macrolide antibiotics using the force field toolkit.	macrolides are an important class of antibiotics that target the bacterial ribosome. computer simulations of macrolides are limited as specific force field parameters have not been previously developed for them. here, we determine charmm-compatible force field parameters for erythromycin, azithromycin, and telithromycin, using the force field toolkit (fftk) plugin in vmd. because of their large size, novel approaches for parametrizing them had to be developed. two methods for determining partial ...	2015	26280362
knowledge-based discovery for designing crispr-cas systems against invading mobilomes in thermophiles.	clustered regularly interspaced short palindromic repeats (crisprs) are direct features of the prokaryotic genomes involved in resistance to their bacterial viruses and phages. herein, we have identified crispr loci together with crispr-associated sequences (cas) genes to reveal their immunity against genome invaders in the thermophilic archaea and bacteria. genomic survey of this study implied that genomic distribution of crispr-cas systems was varied from strain to strain, which was determined ...	2015	26279704
structural basis for the atp-dependent configuration of adenylation active site in bacillus subtilis o-succinylbenzoyl-coa synthetase.	o-succinylbenzoyl-coa synthetase, or mene, is an essential adenylate-forming enzyme targeted for development of novel antibiotics in the menaquinone biosynthesis. using its crystal structures in a ligand-free form or in complex with nucleotides, a conserved pattern is identified in the interaction between atp and adenylating enzymes, including acyl/aryl-coa synthetases, adenylation domains of nonribosomal peptide synthetases, and luciferases. it involves tight gripping interactions of the phosph ...	2015	26276389
from genome to structure and back again: a family portrait of the transcarbamylases.	enzymes in the transcarbamylase family catalyze the transfer of a carbamyl group from carbamyl phosphate (cp) to an amino group of a second substrate. the two best-characterized members, aspartate transcarbamylase (atcase) and ornithine transcarbamylase (otcase), are present in most organisms from bacteria to humans. recently, structures of four new transcarbamylase members, n-acetyl-l-ornithine transcarbamylase (aotcase), n-succinyl-l-ornithine transcarbamylase (sotcase), ygew encoded transcarb ...	2015	26274952
recent advances in biosynthetic modeling of nitric oxide reductases and insights gained from nuclear resonance vibrational and other spectroscopic studies.	this forum article focuses on recent advances in structural and spectroscopic studies of biosynthetic models of nitric oxide reductases (nors). nors are complex metalloenzymes found in the denitrification pathway of earth's nitrogen cycle where they catalyze the proton-dependent two-electron reduction of nitric oxide (no) to nitrous oxide (n2o). while much progress has been made in biochemical and biophysical studies of native nors and their variants, a clear mechanistic understanding of this im ...	2015	26274098
allosteric activation of bacterial swi2/snf2 (switch/sucrose non-fermentable) protein rapa by rna polymerase: biochemical and structural studies.	members of the swi2/snf2 (switch/sucrose non-fermentable) family depend on their atpase activity to mobilize nucleic acid-protein complexes for gene expression. in bacteria, rapa is an rna polymerase (rnap)-associated swi2/snf2 protein that mediates rnap recycling during transcription. it is known that the atpase activity of rapa is stimulated by its interaction with rnap. it is not known, however, how the rapa-rnap interaction activates the enzyme. previously, we determined the crystal structur ...	2015	26272746
degenerate connective polypeptide 1 (cp1) domain from human mitochondrial leucyl-trna synthetase.	the connective polypeptide 1 (cp1) editing domain of leucyl-trna synthetase (leurs) from various species either harbors a conserved active site to exclude trna mis-charging with noncognate amino acids or is evolutionarily truncated or lost because there is no requirement for high translational fidelity. however, human mitochondrial leurs (hmtleurs) contains a full-length but degenerate cp1 domain that has mutations in some residues important for post-transfer editing. the significance of such an ...	2015	26272616
collaborative protein filaments.	it is now well established that prokaryotic cells assemble diverse proteins into dynamic cytoskeletal filaments that perform essential cellular functions. although most of the filaments assemble on their own to form higher order structures, growing evidence suggests that there are a number of prokaryotic proteins that polymerise only in the presence of a matrix such as dna, lipid membrane or even another filament. matrix-assisted filament systems are frequently nucleotide dependent and cytomotiv ...	2015	26271102
a conserved histidine in switch-ii of ef-g moderates release of inorganic phosphate.	elongation factor g (ef-g), a translational gtpase responsible for trna-mrna translocation possesses a conserved histidine (h91 in escherichia coli) at the apex of switch-ii, which has been implicated in gtpase activation and gtp hydrolysis. while h91a, h91r and h91e mutants showed different degrees of defect in ribosome associated gtp hydrolysis, h91q behaved like the wt. however, all these mutants, including h91q, are much more defective in inorganic phosphate (pi) release, thereby suggesting ...	2015	26264741
the photochemical mechanism of a b12-dependent photoreceptor protein.	the coenzyme b12-dependent photoreceptor protein, carh, is a bacterial transcriptional regulator that controls the biosynthesis of carotenoids in response to light. on binding of coenzyme b12 the monomeric apoprotein forms tetramers in the dark, which bind operator dna thus blocking transcription. under illumination the carh tetramer dissociates, weakening its affinity for dna and allowing transcription. the mechanism by which this occurs is unknown. here we describe the photochemistry in carh t ...	2015	26264192
molecular basis of ribosome recognition and mrna hydrolysis by the e. coli yafq toxin.	bacterial type ii toxin-antitoxin modules are protein-protein complexes whose functions are finely tuned by rapidly changing environmental conditions. e. coli toxin yafq is suppressed under steady state growth conditions by virtue of its interaction with its cognate antitoxin, dinj. during stress, dinj is proteolytically degraded and free yafq halts translation by degrading ribosome-bound mrna to slow growth until the stress has passed. although structures of the ribosome with toxins rele and yo ...	2015	26261214
initiation of mrna translation in bacteria: structural and dynamic aspects.	initiation of mrna translation is a major checkpoint for regulating level and fidelity of protein synthesis. being rate limiting in protein synthesis, translation initiation also represents the target of many post-transcriptional mechanisms regulating gene expression. the process begins with the formation of an unstable 30s pre-initiation complex (30s pre-ic) containing initiation factors (ifs) if1, if2 and if3, the translation initiation region of an mrna and initiator fmet-trna whose codon and ...	2015	26259514
multiple conversion between the genes encoding bacterial class-i release factors.	bacteria require two class-i release factors, rf1 and rf2, that recognize stop codons and promote peptide release from the ribosome. rf1 and rf2 were most likely established through gene duplication followed by altering their stop codon specificities in the common ancestor of extant bacteria. this scenario expects that the two rf gene families have taken independent evolutionary trajectories after the ancestral gene duplication event. however, we here report two independent cases of conversion b ...	2015	26257102
linkage of catalysis and 5' end recognition in ribonuclease rnase j.	in diverse bacterial species, the turnover and processing of many rnas is mediated by the ribonuclease rnase j, a member of the widely occurring metallo-β-lactamase enzyme family. we present crystal structures of streptomyces coelicolor rnase j with bound rna in pre- and post-cleavage states, at 2.27 å and 2.80 å resolution, respectively. these structures reveal snapshots of the enzyme cleaving substrate directionally and sequentially from the 5' terminus. in the pre-cleavage state, a water mole ...	2015	26253740
crucial hsp70 co-chaperone complex unlocks metazoan protein disaggregation.	protein aggregates are the hallmark of stressed and ageing cells, and characterize several pathophysiological states. healthy metazoan cells effectively eliminate intracellular protein aggregates, indicating that efficient disaggregation and/or degradation mechanisms exist. however, metazoans lack the key heat-shock protein disaggregase hsp100 of non-metazoan hsp70-dependent protein disaggregation systems, and the human hsp70 system alone, even with the crucial hsp110 nucleotide exchange factor, ...	2015	26245380
activation of gtp hydrolysis in mrna-trna translocation by elongation factor g.	during protein synthesis, elongation of the polypeptide chain by each amino acid is followed by a translocation step in which mrna and transfer rna (trna) are advanced by one codon. this crucial step is catalyzed by elongation factor g (ef-g), a guanosine triphosphatase (gtpase), and accompanied by a rotation between the two ribosomal subunits. a mutant of ef-g, h91a, renders the factor impaired in guanosine triphosphate (gtp) hydrolysis and thereby stabilizes it on the ribosome. we use cryogeni ...	2015	26229983
implication from the predicted docked interaction of sigma h and exploration of its interaction with rna polymerase in mycobacterium tuberculosis.	m. tuberculosis is adapted to remain active in the extreme environmental condition due to the presence of atypical sigma factors commonly called extra cytoplasmic function (ecf) sigma factors. among the 13 sigma factors of m. tuberculosis, 10 are regarded as the ecf sigma factor that exerts their attributes in various stress response. therefore it is of interest to describe the structural prediction of one of the ecf sigma factors, sigma h (sigh), involved in oxidative and heat stress having int ...	2015	26229290
x-ray structure determination using low-resolution electron microscopy maps for molecular replacement.	structures of multisubunit macromolecular machines are primarily determined either by electron microscopy (em) or by x-ray crystallography. in many cases, a structure for a complex can be obtained at low resolution (at a coarse level of detail) with em and at a higher resolution (with finer detail) by x-ray crystallography. the integration of these two structural techniques is becoming increasingly important for the generation of atomic models of macromolecular complexes. a low-resolution em ima ...	2015	26226459
ratcheting of rna polymerase toward structural principles of rna polymerase operations.	rna polymerase (rnap) performs various tasks during transcription by changing its conformational states, which are gradually becoming clarified. a recent study focusing on the conformational transition of rnap between the ratcheted and tight forms illuminated the structural principles underlying its functional operations.	2015	26226152
biochemical and structural properties of a thermostable mercuric ion reductase from metallosphaera sedula.	mercuric ion reductase (mera), a mercury detoxification enzyme, has been tuned by evolution to have high specificity for mercuric ions (hg(2+)) and to catalyze their reduction to a more volatile, less toxic elemental form. here, we present a biochemical and structural characterization of mera from the thermophilic crenarchaeon metallosphaera sedula. mera from m. sedula is a thermostable enzyme, and remains active after extended incubation at 97°c. at 37°c, the nadph oxidation-linked hg(2+) reduc ...	2015	26217660
structures and functions of the multiple kow domains of transcription elongation factor spt5.	the eukaryotic spt4-spt5 heterodimer forms a higher-order complex with rna polymerase ii (and i) to regulate transcription elongation. extensive genetic and functional data have revealed diverse roles of spt4-spt5 in coupling elongation with chromatin modification and rna-processing pathways. a mechanistic understanding of the diverse functions of spt4-spt5 is hampered by challenges in resolving the distribution of functions among its structural domains, including the five kow domains in spt5, a ...	2015	26217010
profile of dinshaw j. patel.		2015	26216951
complete genome sequence and description of salinispira pacifica gen. nov., sp. nov., a novel spirochaete isolated form a hypersaline microbial mat.	during a study of the anaerobic microbial community of a lithifying hypersaline microbial mat of lake 21 on the kiritimati atoll (kiribati republic, central pacific) strain l21-rpul-d2(t) was isolated. the closest phylogenetic neighbor was spirochaeta africana z-7692(t) that shared a 16s rrna gene sequence identity value of 90% with the novel strain and thus was only distantly related. a comprehensive polyphasic study including determination of the complete genome sequence was initiated to chara ...	2015	26203324
trna recognition by a bacterial trna xm32 modification enzyme from the spout methyltransferase superfamily.	trmj proteins from the spout methyltransferase superfamily are trna xm32 modification enzymes that occur in bacteria and archaea. unlike archaeal trmj, bacterial trmj require full-length trna molecules as substrates. it remains unknown how bacterial trmjs recognize substrate trnas and specifically catalyze a 2'-o modification at ribose 32. herein, we demonstrate that all six escherichia coli (ec) trnas with 2'-o-methylated nucleosides at position 32 are substrates of ectrmj, and we show that the ...	2015	26202969
cbr antimicrobials inhibit rna polymerase via at least two bridge-helix cap-mediated effects on nucleotide addition.	rna polymerase inhibitors like the cbr class that target the enzyme's complex catalytic center are attractive leads for new antimicrobials. catalysis by rna polymerase involves multiple rearrangements of bridge helix, trigger loop, and active-center side chains that isomerize the triphosphate of bound ntp and two mg(2+) ions from a preinsertion state to a reactive configuration. cbr inhibitors target a crevice between the n-terminal portion of the bridge helix and a surrounding cap region within ...	2015	26195788
recf and recr play critical roles in the homologous recombination and single-strand annealing pathways of mycobacteria.	mycobacteria encode three dna double-strand break repair pathways: (i) reca-dependent homologous recombination (hr), (ii) ku-dependent nonhomologous end joining (nhej), and (iii) recbcd-dependent single-strand annealing (ssa). mycobacterial hr has two presynaptic pathway options that rely on the helicase-nuclease adnab and the strand annealing protein reco, respectively. ablation of adnab or reco individually causes partial impairment of hr, but loss of adnab and reco in combination abolishes hr ...	2015	26195593
broken symmetry dft calculations/analysis for oxidized and reduced dinuclear center in cytochrome c oxidase: relating structures, protonation states, energies, and mössbauer properties in ba3 thermus thermophilus.	the fea3(3+)···cub(2+) dinuclear center (dnc) structure of the as-isolated oxidized ba3 cytochrome c oxidase (cco) from thermus thermophilus (tt) is still not fully understood. when the proteins are initially crystallized in the oxidized state, they typically become radiolyticly reduced through x-ray irradiation. several x-ray crystal structures of reduced ba3 cco from tt are available. however, depending on whether the crystals were prepared in a lipidic cubic phase environment or in detergent ...	2015	26192749
structural basis of transcription inhibition by cbr hydroxamidines and cbr pyrazoles.	cbr hydroxamidines are small-molecule inhibitors of bacterial rna polymerase (rnap) discovered through high-throughput screening of synthetic-compound libraries. cbr pyrazoles are structurally related rnap inhibitors discovered through scaffold hopping from cbr hydroxamidines. cbr hydroxamidines and pyrazoles selectively inhibit gram-negative bacterial rnap and exhibit selective antibacterial activity against gram-negative bacteria. here, we report crystal structures of the prototype cbr hydroxa ...	2015	26190576
star3d: a stack-based rna 3d structural alignment tool.	the various roles of versatile non-coding rnas typically require the attainment of complex high-order structures. therefore, comparing the 3d structures of rna molecules can yield in-depth understanding of their functional conservation and evolutionary history. recently, many powerful tools have been developed to align rna 3d structures. although some methods rely on both backbone conformations and base pairing interactions, none of them consider the entire hierarchical formation of the rna seco ...	2015	26184875
md simulations of trna and aminoacyl-trna synthetases: dynamics, folding, binding, and allostery.	while trna and aminoacyl-trna synthetases are classes of biomolecules that have been extensively studied for decades, the finer details of how they carry out their fundamental biological functions in protein synthesis remain a challenge. recent molecular dynamics (md) simulations are verifying experimental observations and providing new insight that cannot be addressed from experiments alone. throughout the review, we briefly discuss important historical events to provide a context for how far t ...	2015	26184179
structural basis for methyl-donor-dependent and sequence-specific binding to trna substrates by knotted methyltransferase trmd.	the deep trefoil knot architecture is unique to the spou and trna methyltransferase d (trmd) (spout) family of methyltransferases (mtases) in all three domains of life. in bacteria, trmd catalyzes the n(1)-methylguanosine (m(1)g) modification at position 37 in transfer rnas (trnas) with the (36)gg(37) sequence, using s-adenosyl-l-methionine (adomet) as the methyl donor. the m(1)g37-modified trna functions properly to prevent +1 frameshift errors on the ribosome. here we report the crystal struct ...	2015	26183229
the borrelia afzelii outer membrane protein bapko_0422 binds human factor-h and is predicted to form a membrane-spanning β-barrel.	the deep evolutionary history of the spirochetes places their branch point early in the evolution of the diderms, before the divergence of the present day proteobacteria. as a spirochete, the morphology of the borrelia cell envelope shares characteristics of both gram-positive and gram-negative bacteria. a thin layer of peptidoglycan, tightly associated with the cytoplasmic membrane, is surrounded by a more labile outer membrane (om). this om is rich in lipoproteins but with few known integral m ...	2015	26181365
acylation of biomolecules in prokaryotes: a widespread strategy for the control of biological function and metabolic stress.	acylation of biomolecules (e.g., proteins and small molecules) is a process that occurs in cells of all domains of life and has emerged as a critical mechanism for the control of many aspects of cellular physiology, including chromatin maintenance, transcriptional regulation, primary metabolism, cell structure, and likely other cellular processes. although this review focuses on the use of acetyl moieties to modify a protein or small molecule, it is clear that cells can use many weak organic aci ...	2015	26179745
defining the domain arrangement of the mammalian target of rapamycin complex component rictor protein.	mammalian target of rapamycin (mtor) complexes play a pivotal role in the cell. raptor and rictor proteins interact with mtor to form two distinct complexes, mtorc1 and mtorc2, respectively. while the domain structure of raptor is known, current bioinformatics tools failed to classify the domains in rictor. here we focus on identifying specific domains in rictor by searching for conserved regions. we scanned the pdb structural database and constructed three protein domain datasets. next we carri ...	2015	26176550
structure and evolution of the archaeal lipid synthesis enzyme sn-glycerol-1-phosphate dehydrogenase.	one of the most critical events in the origins of cellular life was the development of lipid membranes. archaea use isoprenoid chains linked via ether bonds to sn-glycerol 1-phosphate (g1p), whereas bacteria and eukaryotes use fatty acids attached via ester bonds to enantiomeric sn-glycerol 3-phosphate. nad(p)h-dependent g1p dehydrogenase (g1pdh) forms g1p and has been proposed to have played a crucial role in the speciation of the archaea. we present here, to our knowledge, the first structures ...	2015	26175150
characterization of a mannose-6-phosphate isomerase from bacillus amyloliquefaciens and its application in fructose-6-phosphate production.	the bam6pi gene encoding a mannose-6-phosphate isomerase (m6pi, ec 5.3.1.8) was cloned from bacillus amyloliquefaciens dsm7 and overexpressed in escherichia coli. the enzyme activity of bam6pi was optimal at ph and temperature of 7.5 and 70°c, respectively, with a kcat/km of 13,900 s-1 mm-1 for mannose-6-phosphate (m6p). the purified bam6pi demonstrated the highest catalytic efficiency of all characterized m6pis. although m6pis have been characterized from several other sources, bam6pi is distin ...	2015	26171785
cautions about the reliability of pairwise gene correlations based on expression data.	rapid growth in the availability of genome-wide transcript abundance levels through gene expression microarrays and rnaseq promises to provide deep biological insights into the complex, genome-wide transcriptional behavior of single-celled organisms. however, this promise has not yet been fully realized.	2015	26167162
enhancement of e. coli acyl-coa synthetase fadd activity on medium chain fatty acids.	fadd catalyses the first step in e. coli beta-oxidation, the activation of free fatty acids into acyl-coa thioesters. this activation makes fatty acids competent for catabolism and reduction into derivatives like alcohols and alkanes. alcohols and alkanes derived from medium chain fatty acids (mcfas, 6-12 carbons) are potential biofuels; however, fadd has low activity on mcfas. herein, we generate mutations in fadd that enhance its acyl-coa synthetase activity on mcfas. homology modeling reveals ...	2015	26157619
the extended at-hook is a novel rna binding motif.	the at-hook has been defined as a dna binding peptide motif that contains a glycine-arginine-proline (g-r-p) tripeptide core flanked by basic amino acids. recent reports documented variations in the sequence of at-hooks and revealed rna binding activity of some canonical at-hooks, suggesting a higher structural and functional variability of this protein domain than previously anticipated. here we describe the discovery and characterization of the extended at-hook peptide motif (eat-hook), in whi ...	2015	26156556
crystal structures of a hyperthermophilic archaeal homoserine dehydrogenase suggest a novel cofactor binding mode for oxidoreductases.	nad(p)-dependent dehydrogenases differ according to their coenzyme preference: some prefer nad, others nadp, and still others exhibit dual cofactor specificity. the structure of a newly identified archaeal homoserine dehydrogenase showed this enzyme to have a strong preference for nadp. however, nadp did not act as a cofactor with this enzyme, but as a strong inhibitor of nad-dependent homoserine oxidation. structural analysis and site-directed mutagenesis showed that the large number of interac ...	2015	26154028
structure and mechanism of the atpase that powers viral genome packaging.	many viruses package their genomes into procapsids using an atpase machine that is among the most powerful known biological motors. however, how this motor couples atp hydrolysis to dna translocation is still unknown. here, we introduce a model system with unique properties for studying motor structure and mechanism. we describe crystal structures of the packaging motor atpase domain that exhibit nucleotide-dependent conformational changes involving a large rotation of an entire subdomain. we al ...	2015	26150523
phenotypic suppression of streptomycin resistance by mutations in multiple components of the translation apparatus.	the bacterial ribosome and its associated translation factors are frequent targets of antibiotics, and antibiotic resistance mutations have been found in a number of these components. such mutations can potentially interact with one another in unpredictable ways, including the phenotypic suppression of one mutation by another. these phenotypic interactions can provide evidence of long-range functional interactions throughout the ribosome and its functional complexes and potentially give insights ...	2015	26148717
expression, purification, crystallization and crystallographic study of lutzomyia longipalpis ljl143.	leishmaniasis is a neglected vector-borne disease with a global prevalence of over 12 million cases and 59,000 annual deaths. transmission of the parasite requires salivary proteins, including ljl143 from the new world sandfly lutzomyia longipalpis. ljl143 is a known marker of sandfly exposure in zoonotic hosts. ljl143 was crystallized from soluble protein expressed using pichia pastoris. x-ray data were collected to 2.6 å resolution from orthorhombic crystals belonging to space group p2(1)2(1)2 ...	2015	26144240
from bacterial to human dihydrouridine synthase: automated structure determination.	the reduction of uridine to dihydrouridine at specific positions in trna is catalysed by dihydrouridine synthase (dus) enzymes. increased expression of human dihydrouridine synthase 2 (hdus2) has been linked to pulmonary carcinogenesis, while its knockdown decreased cancer cell line viability, suggesting that it may serve as a valuable target for therapeutic intervention. here, the x-ray crystal structure of a construct of hdus2 encompassing the catalytic and trna-recognition domains (residues 1 ...	2015	26143927
a dynamic search process underlies microrna targeting.	argonaute proteins play a central role in mediating post-transcriptional gene regulation by micrornas (mirnas). argonautes use the nucleotide sequences in mirnas as guides for identifying target messenger rnas for repression. here, we used single-molecule fret to directly visualize how human argonaute-2 (ago2) searches for and identifies target sites in rnas complementary to its mirna guide. our results suggest that ago2 initially scans for target sites with complementarity to nucleotides 2-4 of ...	2015	26140593
single-molecule imaging reveals that argonaute reshapes the binding properties of its nucleic acid guides.	argonaute proteins repress gene expression and defend against foreign nucleic acids using short rnas or dnas to specify the correct target rna or dna sequence. we have developed single-molecule methods to analyze target binding and cleavage mediated by the argonaute:guide complex, risc. we find that both eukaryotic and prokaryotic argonaute proteins reshape the fundamental properties of rna:rna, rna:dna, and dna:dna hybridization—a small rna or dna bound to argonaute as a guide no longer follows ...	2015	26140592
ecophysiology of an uncultivated lineage of aigarchaeota from an oxic, hot spring filamentous 'streamer' community.	the candidate archaeal phylum 'aigarchaeota' contains microorganisms from terrestrial and subsurface geothermal ecosystems. the phylogeny and metabolic potential of aigarchaeota has been deduced from several recent single-cell amplified genomes; however, a detailed description of their metabolic potential and in situ transcriptional activity is absent. here, we report a comprehensive metatranscriptome-based reconstruction of the in situ metabolism of aigarchaeota in an oxic, hot spring filamento ...	2015	26140529
ecophysiology of an uncultivated lineage of aigarchaeota from an oxic, hot spring filamentous 'streamer' community.	the candidate archaeal phylum 'aigarchaeota' contains microorganisms from terrestrial and subsurface geothermal ecosystems. the phylogeny and metabolic potential of aigarchaeota has been deduced from several recent single-cell amplified genomes; however, a detailed description of their metabolic potential and in situ transcriptional activity is absent. here, we report a comprehensive metatranscriptome-based reconstruction of the in situ metabolism of aigarchaeota in an oxic, hot spring filamento ...	2015	26140529
structural basis for the interconversion of maltodextrins by malq, the amylomaltase of escherichia coli.	amylomaltase malq is essential for the metabolism of maltose and maltodextrins in escherichia coli. it catalyzes transglycosylation/disproportionation reactions in which glycosyl or dextrinyl units are transferred among linear maltodextrins of various lengths. to elucidate the molecular basis of transglycosylation by malq, we have determined three crystal structures of this enzyme, i.e. the apo-form, its complex with maltose, and an inhibitor complex with the transition state analog acarviosine- ...	2015	26139606
mutations of c19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial ca²⁺.	mutations in c19orf12 have been identified in patients affected by neurodegeneration with brain iron accumulation (nbia), a clinical entity characterized by iron accumulation in the basal ganglia. by using western blot analysis with specific antibody and confocal studies, we showed that wild-type c19orf12 protein was not exclusively present in mitochondria, but also in the endoplasmic reticulum (er) and mam (mitochondria associated membrane), while mutant c19orf12 variants presented a different ...	2015	26136767
constraining the lateral helix of respiratory complex i by cross-linking does not impair enzyme activity or proton translocation.	complex i (nadh:ubiquinone oxidoreductase) is a multisubunit, membrane-bound enzyme of the respiratory chain. the energy from nadh oxidation in the peripheral region of the enzyme is used to drive proton translocation across the membrane. one of the integral membrane subunits, nuol in escherichia coli, has an unusual lateral helix of ∼75 residues that lies parallel to the membrane surface and has been proposed to play a mechanical role as a piston during proton translocation (efremov, r. g., bar ...	2015	26134569
identifying novel sequence variants of rna 3d motifs.	predicting rna 3d structure from sequence is a major challenge in biophysics. an important sub-goal is accurately identifying recurrent 3d motifs from rna internal and hairpin loop sequences extracted from secondary structure (2d) diagrams. we have developed and validated new probabilistic models for 3d motif sequences based on hybrid stochastic context-free grammars and markov random fields (scfg/mrf). the scfg/mrf models are constructed using atomic-resolution rna 3d structures. to parameteriz ...	2015	26130723
structural mapping of the clpb atpases of plasmodium falciparum: targeting protein folding and secretion for antimalarial drug design.	caseinolytic chaperones and proteases (clp) belong to the aaa+ protein superfamily and are part of the protein quality control machinery in cells. the eukaryotic parasite plasmodium falciparum, the causative agent of malaria, has evolved an elaborate network of clp proteins including two distinct clpb atpases. clpb1 and clpb2 are involved in different aspects of parasitic proteostasis. clpb1 is present in the apicoplast, a parasite-specific and plastid-like organelle hosting various metabolic pa ...	2015	26130467
the ribosomal s10 protein is a general target for decreased tigecycline susceptibility.	tigecycline is a translational inhibitor with efficacy against a wide range of pathogens. using experimental evolution, we adapted acinetobacter baumannii, enterococcus faecium, escherichia coli, and staphylococcus aureus to growth in elevated tigecycline concentrations. at the end of adaptation, 35 out of 47 replicate populations had clones with a mutation in rpsj, the gene that encodes the ribosomal s10 protein. to validate the role of mutations in rpsj in conferring tigecycline resistance, we ...	2015	26124155
identification of chemical compounds that inhibit the function of glutamyl-trna synthetase from pseudomonas aeruginosa.	pseudomonas aeruginosa glutamyl-trna synthetase (glurs) was overexpressed in escherichia coli. sequence analysis indicated that p. aeruginosa glurs is a discriminating glurs and, similar to other glurs proteins, requires the presence of trna(glu) to produce a glutamyl-amp intermediate. kinetic parameters for interaction with trna were determined and the k(cat) and km were 0.8 s(-1) and 0.68 µm, respectively, resulting in a k(cat)/km of 1.18 s(-1) µm(-1). a robust aminoacylation-based scintillati ...	2015	26116192
transcriptional slippage in the positive-sense rna virus family potyviridae.	the family potyviridae encompasses ~30% of plant viruses and is responsible for significant economic losses worldwide. recently, a small overlapping coding sequence, termed pipo, was found to be conserved in the genomes of all potyvirids. pipo is expressed as part of a frameshift protein, p3n-pipo, which is essential for virus cell-to-cell movement. however, the frameshift expression mechanism has hitherto remained unknown. here, we demonstrate that transcriptional slippage, specific to the vira ...	2015	26113364
specificity and catalysis hardwired at the rna-protein interface in a translational proofreading enzyme.	proofreading modules of aminoacyl-trna synthetases are responsible for enforcing a high fidelity during translation of the genetic code. they use strategically positioned side chains for specifically targeting incorrect aminoacyl-trnas. here, we show that a unique proofreading module possessing a d-aminoacyl-trna deacylase fold does not use side chains for imparting specificity or for catalysis, the two hallmark activities of enzymes. we show, using three distinct archaea, that a side-chain-stri ...	2015	26113036
identification of determinants for trna substrate recognition by escherichia coli c/u34 2'-o-methyltransferase.	post-transcriptional modifications bring chemical diversity to trnas, especially at positions 34 and 37 of the anticodon stem-loop (asl). trml is the prokaryotic methyltransferase that catalyzes the transfer of the methyl group from s-adenosyl-l-methionine to the wobble base of trna(leu)caa and trna(leu)uaa isoacceptors. this cm34/um34 modification affects codon-anticodon interactions and is essential for translational fidelity. trml-catalyzed 2'-o-methylation requires its homodimerization; howe ...	2015	26106808
developmentally regulated heart stopper, a mitochondrially targeted l18 ribosomal protein gene, is required for cell division, differentiation, and seed development in arabidopsis.	evidence is presented for the role of a mitochondrial ribosomal (mitoribosomal) l18 protein in cell division, differentiation, and seed development after the characterization of a recessive mutant, heart stopper (hes). the hes mutant produced uncellularized endosperm and embryos arrested at the late globular stage. the mutant embryos differentiated partially on rescue medium with some forming callus. hes (at1g08845) encodes a mitochondrially targeted member of a highly diverged l18 ribosomal pro ...	2015	26105995
a replisome's journey through the bacterial chromosome.	genome duplication requires the coordinated activity of a multi-component machine, the replisome. in contrast to the background of metabolic diversity across the bacterial domain, the composition and architecture of the bacterial replisome seem to have suffered few changes during evolution. this immutability underlines the replisome's efficiency in copying the genome. it also highlights the success of various strategies inherent to the replisome for responding to stress and avoiding problems dur ...	2015	26097470
thiophenecarboxamide derivatives activated by etha kill mycobacterium tuberculosis by inhibiting the ctp synthetase pyrg.	to combat the emergence of drug-resistant strains of mycobacterium tuberculosis, new antitubercular agents and novel drug targets are needed. phenotypic screening of a library of 594 hit compounds uncovered two leads that were active against m. tuberculosis in its replicating, non-replicating, and intracellular states: compounds 7947882 (5-methyl-n-(4-nitrophenyl)thiophene-2-carboxamide) and 7904688 (3-phenyl-n-[(4-piperidin-1-ylphenyl)carbamothioyl]propanamide). mutants resistant to both compou ...	2015	26097035
first glycoside hydrolase family 2 enzymes from thermus antranikianii and thermus brockianus with β-glucosidase activity.	two glycoside hydrolase encoding genes (tagh2 and tbgh2) were identified from different thermus species using functional screening. based on amino acid similarities, the enzymes were predicted to belong to glycoside hydrolase (gh) family 2. surprisingly, both enzymes (tagh2 and tbgh2) showed twofold higher activities for the hydrolysis of nitrophenol-linked β-d-glucopyranoside than of -galactopyranoside. specific activities of 3,966 u/mg for tagh2 and 660 u/mg for tbgh2 were observed. in accorda ...	2015	26090361
the electronic state of flavoproteins: investigations with proton electron-nuclear double resonance.	electron-nuclear double resonance (endor) spectroscopy provides useful information on hyperfine interactions between nuclear magnetic moments and the magnetic moment of an unpaired electron spin. because the hyperfine coupling constant reacts quite sensitively to polarity changes in the direct vicinity of the nucleus under consideration, endor spectroscopy can be favorably used for the detection of subtle protein-cofactor interactions. a number of pulsed endor studies on flavoproteins have been ...	2009	26089595
the electronic state of flavoproteins: investigations with proton electron-nuclear double resonance.	electron-nuclear double resonance (endor) spectroscopy provides useful information on hyperfine interactions between nuclear magnetic moments and the magnetic moment of an unpaired electron spin. because the hyperfine coupling constant reacts quite sensitively to polarity changes in the direct vicinity of the nucleus under consideration, endor spectroscopy can be favorably used for the detection of subtle protein-cofactor interactions. a number of pulsed endor studies on flavoproteins have been ...	2009	26089595
mutations of ribosomal protein s5 suppress a defect in late-30s ribosomal subunit biogenesis caused by lack of the rbfa biogenesis factor.	the in vivo assembly of ribosomal subunits requires assistance by maturation proteins that are not part of mature ribosomes. one such protein, rbfa, associates with the 30s ribosomal subunits. loss of rbfa causes cold sensitivity and defects of the 30s subunit biogenesis and its overexpression partially suppresses the dominant cold sensitivity caused by a c23u mutation in the central pseudoknot of 16s rrna, a structure essential for ribosome function. we have isolated suppressor mutations that r ...	2015	26089326
co-chaperone specificity in gating of the polypeptide conducting channel in the membrane of the human endoplasmic reticulum.	in mammalian cells, signal peptide-dependent protein transport into the endoplasmic reticulum (er) is mediated by a dynamic polypeptide-conducting channel, the heterotrimeric sec61 complex. previous work has characterized the sec61 complex as a potential er ca(2+) leak channel in hela cells and identified er lumenal molecular chaperone immunoglobulin heavy-chain-binding protein (bip) as limiting ca(2+) leakage via the open sec61 channel by facilitating channel closing. this bip activity involves ...	2015	26085089
the orisome: structure and function.	during the cell division cycle of all bacteria, dna-protein complexes termed orisomes trigger the onset of chromosome duplication. orisome assembly is both staged and stringently regulated to ensure that dna synthesis begins at a precise time and only once at each origin per cycle. orisomes comprise multiple copies of the initiator protein dnaa, which oligomerizes after interacting with specifically positioned recognition sites in the unique chromosomal replication origin, oric. since dnaa is hi ...	2015	26082765
structural organization of enzymes of the phenylacetate catabolic hybrid pathway.	aromatic compounds are the second most abundant class of molecules on the earth and frequent environmental pollutants. they are difficult to metabolize due to an inert chemical structure, and of all living organisms, only microbes have evolved biochemical pathways that can open an aromatic ring and catabolize thus formed organic molecules. in bacterial genomes, the phenylacetate (pa) utilization pathway is abundant and represents the central route for degradation of a variety of organic compound ...	2015	26075354
purification and characterization of dr_2577 (slpa) a major s-layer protein from deinococcus radiodurans.	the protein dr_2577 is a major surface layer component of the radio-resistant bacterium deinococcus radiodurans. in the present study dr_2577 has been purified and its oligomeric profile characterized by means of size exclusion chromatography and gel electrophoresis. dr_2577 was found to be organized into three hierarchical orders characterized by monomers, stable dimers formed by the occurrence of disulfide bonds, and hexamers resulting from a combination of dimers. the structural implications ...	2015	26074883
halophiles and their enzymes: negativity put to good use.	halophilic microorganisms possess stable enzymes that function in very high salinity, an extreme condition that leads to denaturation, aggregation, and precipitation of most other proteins. genomic and structural analyses have established that the enzymes of halophilic archaea and many halophilic bacteria are negatively charged due to an excess of acidic over basic residues, and altered hydrophobicity, which enhance solubility and promote function in low water activity conditions. here, we provi ...	2015	26066288
challenges and opportunities for customizing polyhydroxyalkanoates.	polyhydroxyalkanoates (phas) as an alternative to synthetic plastics have been gaining increasing attention. being natural in their origin, phas are completely biodegradable and eco-friendly. however, consistent efforts to exploit this biopolymer over the last few decades have not been able to pull phas out of their nascent stage, inspite of being the favorite of the commercial world. the major limitations are: (1) the high production cost, which is due to the high cost of the feed and (2) poor ...	2015	26063933
seca: a potential antimicrobial target.	there is a consensus in the medical profession of the pressing need for novel antimicrobial agents due to issues related to drug resistance. in practice, solutions to this problem to a large degree lie with the identification of new and vital targets in bacteria and subsequently designing their inhibitors. we consider seca a very promising antimicrobial target. in this review, we compile and analyze information available on seca to show that inhibition of seca has a multitude of consequences. fu ...	2015	26062397
3-sulfinopropionyl-coenzyme a (3sp-coa) desulfinase from advenella mimigardefordensis dpn7(t): crystal structure and function of a desulfinase with an acyl-coa dehydrogenase fold.	3-sulfinopropionyl-coenzyme a (3sp-coa) desulfinase (acddpn7; ec 3.13.1.4) was identified during investigation of the 3,3'-dithiodipropionic acid (dtdp) catabolic pathway in the betaproteobacterium advenella mimigardefordensis strain dpn7(t). dtdp is an organic disulfide and a precursor for the synthesis of polythioesters (ptes) in bacteria, and is of interest for biotechnological pte production. acddpn7 catalyzes sulfur abstraction from 3sp-coa, a key step during the catabolism of dtdp. here, t ...	2015	26057676
protein synthesis during cellular quiescence is inhibited by phosphorylation of a translational elongation factor.	in nature, most organisms experience conditions that are suboptimal for growth. to survive, cells must fine-tune energy-demanding metabolic processes in response to nutrient availability. here, we describe a novel mechanism by which protein synthesis in starved cells is down-regulated by phosphorylation of the universally conserved elongation factor tu (ef-tu). phosphorylation impairs the essential gtpase activity of ef-tu, thereby preventing its release from the ribosome. as a consequence, phos ...	2015	26056311