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mutations in tubg1, dync1h1, kif5c and kif2a cause malformations of cortical development and microcephaly.the genetic causes of malformations of cortical development (mcd) remain largely unknown. here we report the discovery of multiple pathogenic missense mutations in tubg1, dync1h1 and kif2a, as well as a single germline mosaic mutation in kif5c, in subjects with mcd. we found a frequent recurrence of mutations in dync1h1, implying that this gene is a major locus for unexplained mcd. we further show that the mutations in kif5c, kif2a and dync1h1 affect atp hydrolysis, productive protein folding an ...201323603762
essential requirements for the detection and degradation of invaders by the haloferax volcanii crispr/cas system i-b.to fend off foreign genetic elements, prokaryotes have developed several defense systems. the most recently discovered defense system, crispr/cas, is sequence-specific, adaptive and heritable. the two central components of this system are the cas proteins and the crispr rna. the latter consists of repeat sequences that are interspersed with spacer sequences. the crispr locus is transcribed into a precursor rna that is subsequently processed into short crrnas. crispr/cas systems have been identif ...201323594992
electron transfer mechanism of the rieske protein from thermus thermophilus from solution nuclear magnetic resonance investigations.we report nuclear magnetic resonance (nmr) data indicating that the rieske protein from the cytochrome bc complex of thermus thermophilus (ttrp) undergoes modest redox-state-dependent and ligand-dependent conformational changes. to test models concerning the mechanism by which ttrp transfers between different sites on the complex, we monitored (1)h, (15)n, and (13)c nmr signals as a function of the redox state and molar ratio of added ligand. our studies of full-length ttrp were conducted in the ...201323480240
structural basis for the enzymatic formation of the key strawberry flavor compound 4-hydroxy-2,5-dimethyl-3(2h)-furanone.the last step in the biosynthetic route to the key strawberry flavor compound 4-hydroxy-2,5-dimethyl-3(2h)-furanone (hdmf) is catalyzed by fragaria x ananassa enone oxidoreductase (faeo), earlier putatively assigned as quinone oxidoreductase (faqr). the ripening-induced enzyme catalyzes the reduction of the exocyclic double bond of the highly reactive precursor 4-hydroxy-5-methyl-2-methylene-3(2h)-furanone (hmmf) in a nad(p)h-dependent manner. to elucidate the molecular mechanism of this peculia ...201323589283
crystal structure of a prokaryotic (6-4) photolyase with an fe-s cluster and a 6,7-dimethyl-8-ribityllumazine antenna chromophore.the (6-4) photolyases use blue light to reverse uv-induced (6-4) photoproducts in dna. this (6-4) photorepair was thought to be restricted to eukaryotes. here we report a prokaryotic (6-4) photolyase, phrb from agrobacterium tumefaciens, and propose that (6-4) photolyases are broadly distributed in prokaryotes. the crystal structure of photolyase related protein b (phrb) at 1.45 å resolution suggests a dna binding mode different from that of the eukaryotic counterparts. a his-his-x-x-arg motif i ...201323589886
t box rna decodes both the information content and geometry of trna to affect gene expression.the t box leader sequence is an rna element that controls gene expression by binding directly to a specific trna and sensing its aminoacylation state. this interaction controls expression of amino acid-related genes in a negative feedback loop. the t box rna structure is highly conserved, but its trna binding mechanism is only partially understood. known sequence elements are the specifier sequence, which recognizes the trna anticodon, and the antiterminator bulge, which base pairs with the trna ...201323589841
life in an arsenic-containing gold mine: genome and physiology of the autotrophic arsenite-oxidizing bacterium rhizobium sp. nt-26.arsenic is widespread in the environment and its presence is a result of natural or anthropogenic activities. microbes have developed different mechanisms to deal with toxic compounds such as arsenic and this is to resist or metabolize the compound. here, we present the first reference set of genomic, transcriptomic and proteomic data of an alphaproteobacterium isolated from an arsenic-containing goldmine: rhizobium sp. nt-26. although phylogenetically related to the plant-associated bacteria, t ...201323589360
the yin and yang of trna: proper binding of acceptor end determines the catalytic balance of editing and aminoacylation.faithful translation of the genetic code depends on accurate coupling of amino acids with cognate transfer rnas (trnas) catalyzed by aminoacyl-trna synthetases. the fidelity of leucyl-trna synthetase (leurs) depends mainly on proofreading at the pre- and post-transfer levels. during the catalytic cycle, the trna cca-tail shuttles between the synthetic and editing domains to accomplish the aminoacylation and editing reactions. previously, we showed that the y330d mutation of escherichia coli leur ...201323585282
insight to the interaction of the dihydrolipoamide acetyltransferase (e2) core with the peripheral components in the escherichia coli pyruvate dehydrogenase complex via multifaceted structural approaches.multifaceted structural approaches were undertaken to investigate interaction of the e2 component with e3 and e1 components from the escherichia coli pyruvate dehydrogenase multienzyme complex (pdhc), as a representative of the pdhc from gram-negative bacteria. the crystal structure of e3 at 2.5 å resolution reveals similarity to other e3 structures and was an important starting point for understanding interaction surfaces between e3 and e2. biochemical studies revealed that r129e-e2 and r150e-e ...201323580650
l1r, a27l, a33r and b5r vaccinia virus genes expressed by fowlpox recombinants as putative novel orthopoxvirus vaccines.the traditional smallpox vaccine, administered by scarification, was discontinued in the general population from 1980, because of the absence of new smallpox cases. however, the development of an effective prophylactic vaccine against smallpox is still necessary, to protect from the threat of deliberate release of the variola virus for bioterrorism and from new zoonotic infections, and to improve the safety of the traditional vaccine. preventive vaccination still remains the most effective contr ...201323578094
non-complexed four cascade enzyme mixture: simple purification and synergetic co-stabilization.cell-free biosystems comprised of synthetic enzymatic pathways would be a promising biomanufacturing platform due to several advantages, such as high product yield, fast reaction rate, easy control and access, and so on. however, it was essential to produce (purified) enzymes at low costs and stabilize them for a long time so to decrease biocatalyst costs. we studied the stability of the four recombinant enzyme mixtures, all of which originated from thermophilic microorganisms: triosephosphate i ...201323585905
exclusive use of trans-editing domains prevents proline mistranslation.aminoacyl-trna synthetases (arss) catalyze the attachment of specific amino acids to cognate trnas. although the accuracy of this process is critical for overall translational fidelity, similar sizes of many amino acids provide a challenge to arss. for example, prolyl-trna synthetases (prorss) mischarge alanine and cysteine onto trna(pro). many bacterial prorss possess an alanine-specific proofreading domain (ins) but lack the capability to edit cys-trna(pro). instead, cys-trna(pro) is cleared b ...201323564458
mycobacterium tuberculosis rna polymerase-binding protein a (rbpa) and its interactions with sigma factors.rna polymerase-binding protein a (rbpa), encoded by rv2050, is specific to the actinomycetes, where it is highly conserved. in the pathogen mycobacterium tuberculosis, rbpa is essential for growth and survival. rbpa binds to the β subunit of the rna polymerase where it activates transcription by unknown mechanisms, and it may also influence the response of m. tuberculosis to the current frontline anti-tuberculosis drug rifampicin. here we report the solution structure of rbpa and identify the pr ...201323548911
inhibition of isoleucyl-trna synthetase as a potential treatment for human african trypanosomiasis.trypanosoma brucei sp. causes human african trypanosomiasis (hat; african sleeping sickness). the parasites initially proliferate in the hemolymphatic system and then invade the central nervous system, which is lethal if not treated. new drugs are needed for hat because the approved drugs are few, toxic, and difficult to administer, and drug resistance is spreading. we showed by rnai knockdown that t. brucei isoleucyl-trna synthetase is essential for the parasites in vitro and in vivo in a mouse ...201323548908
metagenomics and novel gene discovery: promise and potential for novel therapeutics.metagenomics provides a means of assessing the total genetic pool of all the microbes in a particular environment, in a culture-independent manner. it has revealed unprecedented diversity in microbial community composition, which is further reflected in the encoded functional diversity of the genomes, a large proportion of which consists of novel genes. herein, we review both sequence-based and functional metagenomic methods to uncover novel genes and outline some of the associated problems of e ...201324317337
metagenomics and novel gene discovery: promise and potential for novel therapeutics.metagenomics provides a means of assessing the total genetic pool of all the microbes in a particular environment, in a culture-independent manner. it has revealed unprecedented diversity in microbial community composition, which is further reflected in the encoded functional diversity of the genomes, a large proportion of which consists of novel genes. herein, we review both sequence-based and functional metagenomic methods to uncover novel genes and outline some of the associated problems of e ...201324317337
rna-methyltransferase trma is a dual-specific enzyme responsible for c5-methylation of uridine in both tmrna and trna.in bacteria, trans-translation rescues stalled ribosomes by the combined action of tmrna (transfer-mrna) and its associated protein smpb. the tmrna 5' and 3' ends fold into a trna-like domain (tld), which shares structural and functional similarities with trnas. as in trnas, the uuc sequence of the t-arm of the tld is post-transcriptionally modified to m (5)uψc. in trnas of gram-negative bacteria, formation of m (5)u is catalyzed by the sam-dependent methyltransferase trma, while formation of m ...201323603891
erythroid heme biosynthesis and its disorders.heme, which is composed of iron and the small organic molecule protoporphyrin, is an essential component of hemoglobin as well as a variety of physiologically important hemoproteins. during erythropoiesis, heme synthesis is induced before, and is essential for, globin synthesis. although all cells possess the ability to synthesize heme, there are distinct differences between regulation of the pathway in developing erythroid cells and all other types of cells. disorders that compromise the abilit ...201323471474
tertiary structure-based analysis of microrna-target interactions.current computational analysis of microrna interactions is based largely on primary and secondary structure analysis. computationally efficient tertiary structure-based methods are needed to enable more realistic modeling of the molecular interactions underlying mirna-mediated translational repression. we incorporate algorithms for predicting duplex rna structures, ionic strength effects, duplex entropy and free energy, and docking of duplex-argonaute protein complexes into a pipeline to model a ...201323417009
trna residues evolved to promote translational accuracy.the decoding properties of 22 structurally conservative base-pair and base-triple mutations in the anticodon hairpin and tertiary core of escherichia coli trna(ala)ggc were determined under single turnover conditions using e. coli ribosomes. while all of the mutations were able to efficiently decode the cognate gcc codon, many showed substantial misreading of near-cognate guc or acc codons. although all the misreading mutations were present in the sequences of other e. coli trnas, they were neve ...201323440350
identification and characterization of mala in the maltose/maltodextrin operon of sulfolobus acidocaldarius dsm639.a putative maltose/maltodextrin operon was found in the sulfolobus acidocaldarius dsm639 genome. the gene cluster consisted of 7 genes (mala, trmb, amya, malg, malf, male, and malk). here, we report the identification of mala, which is responsible for the hydrolysis of maltose or maltodextrin to glucose in s. acidocaldarius. the transcription level of mala was increased 3-fold upon the addition of maltose or starch to the medium. moreover, the α-glucosidase activity for maltose as a substrate in ...201323396915
characterization of the msmeg_2631 gene (mmp) encoding a multidrug and toxic compound extrusion (mate) family protein in mycobacterium smegmatis and exploration of its polyspecific nature using biolog phenotype microarray.in mycobacterium, multidrug efflux pumps can be associated with intrinsic drug resistance. comparison of putative mycobacterial transport genes revealed a single annotated open reading frame (orf) for a multidrug and toxic compound extrusion (mate) family efflux pump in all sequenced mycobacteria except mycobacterium leprae. since mate efflux pumps function as multidrug efflux pumps by conferring resistance to structurally diverse antibiotics and dna-damaging chemicals, we studied this gene (msm ...201323292779
defining the rna-protein interactions in the trypanosome preribosomal complex.in eukaryotes, 5s rrna is transcribed in the nucleoplasm and requires the ribosomal protein l5 to deliver it to the nucleolus for ribosomal assembly. the trypanosome-specific proteins p34 and p37 form a novel preribosomal complex with the eukaryotic conserved l5-5s rrna complex in the nucleoplasm. previous results suggested that p34 acts together with l5 to bridge the interaction with 5s rrna and thus to stabilize 5s rrna, an important role in the early steps of ribosomal biogenesis. here, we ha ...201323397568
the structural basis for specific decoding of aua by isoleucine trna on the ribosome.decoding of the aua isoleucine codon in bacteria and archaea requires modification of a c in the anticodon wobble position of the isoleucine trna. here, we report the crystal structure of the archaeal trna2(ile), which contains the modification agmatidine in its anticodon, in complex with the aua codon on the 70s ribosome. the structure illustrates how agmatidine confers codon specificity for aua over aug.201323542153
specificity of processing α-glucosidase i is guided by the substrate conformation: crystallographic and in silico studies.the enzyme “glui” is key to the synthesis of critical glycoproteins in the cell.201323536181
distinctive contributions of the ribosomal p-site elements m2g966, m5c967 and the c-terminal tail of the s9 protein in the fidelity of initiation of translation in escherichia coli.the accuracy of pairing of the anticodon of the initiator trna (trna(fmet)) and the initiation codon of an mrna, in the ribosomal p-site, is crucial for determining the translational reading frame. however, a direct role of any ribosomal element(s) in scrutinizing this pairing is unknown. the p-site elements, m(2)g966 (methylated by rsmd), m(5)c967 (methylated by rsmb) and the c-terminal tail of the protein s9 lie in the vicinity of trna(fmet). we investigated the role of these elements in initi ...201323530111
comparative proteomics identifies the cell-associated lethality of m. tuberculosis relbe-like toxin-antitoxin complexes.the mycobacterium tuberculosis (mtb) genome encodes approximately 90 toxin-antitoxin protein complexes, including three relbe family members, which are believed to play a major role in bacterial fitness and pathogenicity. we have determined the crystal structures of mtb relbe-2 and relbe-3, and the structures reveal homologous heterotetramers. our structures suggest rele-2, and by extension the closely related rele-1, use a different catalytic mechanism than rele-3, because our analysis of the r ...201323523424
probing the stabilizing effects of modified nucleotides in the bacterial decoding region of 16s ribosomal rna.the bacterial decoding region of 16s ribosomal rna has multiple modified nucleotides. in order to study the role of n(4),2'-o-dimethylcytidine (m(4)cm), the corresponding phosphoramidite was synthesized utilizing 5'-silyl-2'-ace chemistry. using solid-phase synthesis, m(4)cm, 5-methylcytidine (m(5)c), 3-methyluridine (m(3)u), and 2'-o-methylcytidine (cm) were site-specifically incorporated into small rnas representing the decoding regions of different bacterial species. biophysical studies were ...201323566761
leucine-specific domain modulates the aminoacylation and proofreading functional cycle of bacterial leucyl-trna synthetase.the leucine-specific domain (lsd) is a compact well-ordered module that participates in positioning of the conserved kmsks catalytic loop in most leucyl-trna synthetases (leurss). however, the leurs from mycoplasma mobile (mmleurs) has a tetrapeptide gkdg instead of the lsd. here, we show that the tetrapeptide gkdg can confer trna charging and post-transfer editing activity when transplanted into an inactive escherichia coli leurs (ecleurs) that has had its lsd deleted. reciprocally, the lsd, to ...201323525458
exploration of sitagliptin as a potential inhibitor for the m1 alanine aminopeptidase enzyme in plasmodium falciparum using computational docking.plasmodium falciparum has limited capacity for de novo amino acid synthesis and rely on degradation of host hemoglobin to maintain protein metabolism and synthesis of proteins. m1 alanine aminopeptidase enzyme of the parasite involved in the terminal degradation of host hemoglobin was subjected to in silico screening with low molecular weight protease inhibitors. the km (avg) of the enzyme m1 alanine aminopeptidase for the substrate dl - alanine β napthylamide hydrochloride was estimated as 322. ...201323559748
crystal structure of 70s ribosome with both cognate trnas in the e and p sites representing an authentic elongation complex.during the translation cycle, a cognate deacylated trna can only move together with the codon into the e site. we here present the first structure of a cognate trna bound to the ribosomal e site resulting from translocation by ef-g, in which an entire l1 stalk (l1 protein and l1 rrna) interacts with e-site trna (e-trna), representing an authentic ribosome elongation complex. our results revealed that the watson-crick base pairing is formed at the first and second codon-anticodon positions in the ...201323527033
structural insights into putative molybdenum cofactor biosynthesis protein c (moac2) from mycobacterium tuberculosis h37rv.the molybdenum cofactor (moco) biosynthesis pathway is an evolutionary conserved pathway seen in almost all eukaryotes including the pathogenic species mycobacterium tuberculosis. this pathway comprises of several novel reactions which include the initial formation of precursor z from guanosine triphosphate (gtp), catalysed by two enzymes moaa and moac. although moco biosynthesis is well understood, the first step is still not clear. in m. tuberculosis h37rv, three orthologous genes of moac have ...201323526978
uga is an additional glycine codon in uncultured sr1 bacteria from the human microbiota.the composition of the human microbiota is recognized as an important factor in human health and disease. many of our cohabitating microbes belong to phylum-level divisions for which there are no cultivated representatives and are only represented by small subunit rrna sequences. for one such taxon (sr1), which includes bacteria with elevated abundance in periodontitis, we provide a single-cell genome sequence from a healthy oral sample. sr1 bacteria use a unique genetic code. in-frame tga (opal ...201323509275
characterization of halomonas sp. zm3 isolated from the zelazny most post-flotation waste reservoir, with a special focus on its mobile dna.halomonas sp. zm3 was isolated from zelazny most post-flotation mineral waste repository (poland), which is highly contaminated with heavy metals and various organic compounds. mobile dna of the strain (i.e. plasmids and transposons) were analyzed in order to identify genetic information enabling adaptation of the bacterium to the harsh environmental conditions.201323497212
the role of mirnas in regulating gene expression networks.micrornas (mirnas) are key regulators of gene expression. they are conserved across species, expressed across cell types, and active against a large proportion of the transcriptome. the sequence-complementary mechanism of mirna activity exploits combinatorial diversity, a property conducive to network-wide regulation of gene expression, and functional evidence supporting this hypothesized systems-level role has steadily begun to accumulate. the emerging models are exciting and will yield deep in ...201323500488
structural and functional insight into the universal stress protein family.we present the crystal structures of two universal stress proteins (usp) from archaeoglobus fulgidus and nitrosomonas europaea in both apo- and ligand-bound forms. this work is the first complete synthesis of the structural properties of 26 usp available in the protein data bank, over 75% of which were determined by structure genomics centers with no additional information provided. the results of bioinformatic analyses of all available usp structures and their sequence homologs revealed that th ...201323745136
structural units important for activity of a novel-type phosphoserine phosphatase from hydrogenobacter thermophilus tk-6 revealed by crystal structure analysis.novel-type serine-synthesizing enzymes, termed metal-independent phosphoserine phosphatases (ipsps), were recently identified and characterized from hydrogenobacter thermophilus, a chemolithoautotrophic bacterium belonging to the order aquificales. ipsps are cofactor-dependent phosphoglycerate mutase (dpgm)-like phosphatases that have significant amino acid sequence similarity to dpgms but lack phosphoglycerate mutase activity. genes coding dpgm-like phosphatases have been identified in a broad ...201323479726
amino acid substitutions in cold-adapted proteins from halorubrum lacusprofundi, an extremely halophilic microbe from antarctica.the halophilic archaeon halorubrum lacusprofundi, isolated from the perennially cold and hypersaline deep lake in antarctica, was recently sequenced and compared to 12 haloarchaea from temperate climates by comparative genomics. amino acid substitutions for 604 h. lacusprofundi proteins belonging to conserved haloarchaeal orthologous groups (chogs) were determined and found to occur at 7.85% of positions invariant in proteins from mesophilic haloarchaea. the following substitutions were observed ...201323536799
ribonucleoproteins in archaeal pre-rrna processing and modification.given that ribosomes are one of the most important cellular macromolecular machines, it is not surprising that there is intensive research in ribosome biogenesis. ribosome biogenesis is a complex process. the maturation of ribosomal rnas (rrnas) requires not only the precise cleaving and folding of the pre-rrna but also extensive nucleotide modifications. at the heart of the processing and modifications of pre-rrnas in archaea and eukarya are ribonucleoprotein (rnp) machines. they are called sma ...201323554567
crystal and nmr structures give insights into the role and dynamics of subunit f of the eukaryotic v-atpase from saccharomyces cerevisiae.subunit f of v-atpases is proposed to undergo structural alterations during catalysis and reversible dissociation from the v1vo complex. recently, we determined the low resolution structure of f from saccharomyces cerevisiae v-atpase, showing an n-terminal egg shape, connected to a c-terminal hook-like segment via a linker region. to understand the mechanistic role of subunit f of s. cerevisiae v-atpase, composed of 118 amino acids, the crystal structure of the major part of f, f(1-94), was solv ...201323476018
diversity in the origins of proteostasis networks--a driver for protein function in evolution.although the sequence of a protein largely determines its function, proteins can adopt different folding states in response to changes in the environment, some of which may be deleterious to the organism. all organisms--bacteria, archaea and eukarya--have evolved a protein homeostasis, or proteostasis, network comprising chaperones and folding factors, degradation components, signalling pathways and specialized compartmentalized modules that manage protein folding in response to environmental st ...201323463216
recognition and cleavage of a nonstructured crispr rna by its processing endoribonuclease cas6.clustered regularly interspaced short palindromic repeats (crisprs) confer adaptive immunity to prokaryotes through a small rna-mediated mechanism. specific endoribonucleases are required by all crispr-bearing organisms to process crispr rnas into small rna that serve as guides for defensive effector complexes. the molecular mechanism of how the endoribonucleases process the class of crispr rna containing no predicted secondary structural features remains largely elusive. here, we report cocryst ...201323454186
dynamic interplay of para with the polarity protein, scy, coordinates the growth with chromosome segregation in streptomyces coelicolor.prior to bacterial cell division, the atp-dependent polymerization of the cytoskeletal protein, para, positions the newly replicated origin-proximal region of the chromosome by interacting with parb complexes assembled on pars sites located close to the origin. during the formation of unigenomic spores from multi-genomic aerial hyphae compartments of streptomyces coelicolor, para is developmentally triggered to form filaments along the hyphae; this promotes the accurate and synchronized segregat ...201323536551
the plasticity of a structural motif in rna: structural polymorphism of a kink turn as a function of its environment.the k-turn is a widespread structural motif that introduces a tight kink into the helical axis of double-stranded rna. the adenine bases of consecutive g•a pairs are directed toward the minor groove of the opposing helix, hydrogen bonding in a typical a-minor interaction. we show here that the available structures of k-turns divide into two classes, depending on whether n3 or n1 of the adenine at the 2b position accepts a hydrogen bond from the o2' at the -1n position. there is a coordinated str ...201323325110
development of a continuous bioconversion system using a thermophilic whole-cell biocatalyst.the heat treatment of recombinant mesophilic cells having heterologous thermophilic enzymes results in the denaturation of indigenous mesophilic enzymes and the elimination of undesired side reactions; therefore, highly selective whole-cell catalysts comparable to purified enzymes can be readily prepared. however, the thermolysis of host cells leads to the heat-induced leakage of thermophilic enzymes, which are produced as soluble proteins, limiting the exploitation of their excellent stability ...201323335777
discovery of a novel class of boron-based antibacterials with activity against gram-negative bacteria.gram-negative bacteria cause approximately 70% of the infections in intensive care units. a growing number of bacterial isolates responsible for these infections are resistant to currently available antibiotics and to many in development. most agents under development are modifications of existing drug classes, which only partially overcome existing resistance mechanisms. therefore, new classes of gram-negative antibacterials with truly novel modes of action are needed to circumvent these existi ...201323295920
energy functions in de novo protein design: current challenges and future prospects.in the past decade, a concerted effort to successfully capture specific tertiary packing interactions produced specific three-dimensional structures for many de novo designed proteins that are validated by nuclear magnetic resonance and/or x-ray crystallographic techniques. however, the success rate of computational design remains low. in this review, we provide an overview of experimentally validated, de novo designed proteins and compare four available programs, rosettadesign, egad, liang-gris ...201323451890
an engineered heme-copper center in myoglobin: co migration and binding.we have investigated co migration and binding in cubmb, a copper-binding myoglobin double mutant (l29h-f43h), by using fourier transform infrared spectroscopy and flash photolysis over a wide temperature range. this mutant was originally engineered with the aim to mimic the catalytic site of heme-copper oxidases. comparison of the wild-type protein mb and cubmb shows that the copper ion in the distal pocket gives rise to significant effects on ligand binding to the heme iron. in mb and copper-fr ...201323459127
mutyh dna glycosylase: the rationale for removing undamaged bases from the dna.maintenance of genetic stability is crucial for all organisms in order to avoid the onset of deleterious diseases such as cancer. one of the many proveniences of dna base damage in mammalian cells is oxidative stress, arising from a variety of endogenous and exogenous sources, generating highly mutagenic oxidative dna lesions. one of the best characterized oxidative dna lesion is 7,8-dihydro-8-oxoguanine (8-oxo-g), which can give rise to base substitution mutations (also known as point mutations ...201323450852
crystallization and preliminary x-ray analysis of peptidyl-trna hydrolase from thermus thermophilus hb8.peptidyl-trna is produced from the ribosome as a result of aborted translation. peptidyl-trna hydrolase cleaves the ester bond between the peptide and the trna of peptidyl-trna molecules, to recycle trna for further rounds of protein synthesis. in this study, peptidyl-trna hydrolase from thermus thermophilus hb8 (tthpth) was crystallized using 2-methyl-2,4-pentanediol as a precipitant. the crystals belonged to the orthorhombic space group p2₁2₁2₁, with unit-cell parameters a=47.45, b=53.92, c=58 ...201323519816
thermus oshimai jl-2 and t. thermophilus jl-18 genome analysis illuminates pathways for carbon, nitrogen, and sulfur cycling.the complete genomes of thermus oshimai jl-2 and t. thermophilus jl-18 each consist of a circular chromosome, 2.07 mb and 1.9 mb, respectively, and two plasmids ranging from 0.27 mb to 57.2 kb. comparison of the t. thermophilus jl-18 chromosome with those from other strains of t. thermophilus revealed a high degree of synteny, whereas the megaplasmids from the same strains were highly plastic. the t. oshimai jl-2 chromosome and megaplasmids shared little or no synteny with other sequenced thermu ...201324019992
interplay between heat shock proteins hsp101 and hsa32 prolongs heat acclimation memory posttranscriptionally in arabidopsis.heat acclimation improves the tolerance of organisms to severe heat stress. our previous work showed that in arabidopsis (arabidopsis thaliana), the "memory" of heat acclimation treatment decayed faster in the absence of the heat-stress-associated 32-kd protein hsa32, a heat-induced protein predominantly found in plants. the hsa32 null mutant attains normal short-term acquired thermotolerance but is defective in long-term acquired thermotolerance. to further explore this phenomenon, we isolated ...201323439916
effect of heavy atoms on the thermal stability of α-amylase from aspergillus oryzae.currently, there are no versatile and established methods for improving stability of proteins. in an entirely different approach from conventional techniques such as mutagenesis, we attempted to enhance enzyme stability of α-amylase from aspergillus oryzae using a heavy-atom derivatization technique. we evaluated changes in stability using differential scanning calorimetry (dsc). candidate heavy atoms were identified using the heavy-atom database system hatodas, a web-based tool designed to assi ...201323451229
structure of vibrio cholerae ribosome hibernation promoting factor.the x-ray crystal structure of ribosome hibernation promoting factor (hpf) from vibrio cholerae is presented at 2.0 å resolution. the crystal was phased by two-wavelength mad using cocrystallized cobalt. the asymmetric unit contained two molecules of hpf linked by four co atoms. the metal-binding sites observed in the crystal are probably not related to biological function. the structure of hpf has a typical β-α-β-β-β-α fold consistent with previous structures of yfia and hpf from escherichia co ...201323519794
structural basis for potent inhibitory activity of the antibiotic tigecycline during protein synthesis.here we present an x-ray crystallography structure of the clinically relevant tigecycline antibiotic bound to the 70s ribosome. our structural and biochemical analysis indicate that the enhanced potency of tigecycline results from a stacking interaction with nucleobase c1054 within the decoding site of the ribosome. single-molecule fluorescence resonance energy transfer studies reveal that, during decoding, tigecycline inhibits the initial codon recognition step of trna accommodation and prevent ...201323431179
leucyl-trna synthetase editing domain functions as a molecular rheostat to control codon ambiguity in mycoplasma pathogens.mycoplasma leucyl-trna synthetases (leurss) have been identified in which the connective polypeptide 1 (cp1) amino acid editing domain that clears mischarged trnas are missing (mycoplasma mobile) or highly degenerate (mycoplasma synoviae). thus, these enzymes rely on a clearance pathway called pretransfer editing, which hydrolyzes misactivated aminoacyl-adenylate intermediate via a nebulous mechanism that has been controversial for decades. even as the sole fidelity pathway for clearing amino ac ...201323431144
crystal structure of the entire respiratory complex i.complex i is the first and largest enzyme of the respiratory chain and has a central role in cellular energy production through the coupling of nadh:ubiquinone electron transfer to proton translocation. it is also implicated in many common human neurodegenerative diseases. here, we report the first crystal structure of the entire, intact complex i (from thermus thermophilus) at 3.3 å resolution. the structure of the 536-kda complex comprises 16 different subunits, with a total of 64 transmembran ...201323417064
3' fragment of mir173-programmed risc-cleaved rna is protected from degradation in a complex with risc and sgs3.trans-acting small interfering rnas (tasirnas) are plant-specific endogenous sirnas produced via a unique pathway whose first step is the microrna (mirna)-programmed rna-induced silencing complex (risc)-mediated cleavage of tasirna gene (tas) transcripts. one of the products is subsequently transformed into tasirnas by a pathway that requires several factors including suppressor of gene silencing3 (sgs3) and rna-dependent rna polymerase6. here, using in vitro assembled argonaute (ago)1-riscs, we ...201323417299
structure and mechanism of the pilf dna transformation atpase from thermus thermophilus.many gram-negative bacteria contain specific systems for uptake of foreign dna, which play a critical role in the acquisition of antibiotic resistance. the ttpilf (pilf atpase from thermus thermophilus) is required for high transformation efficiency, but its mechanism of action is unknown. in the present study, we show that ttpilf is able to bind to both dna and rna. the structure of ttpilf was determined by cryoelectron microscopy in the presence and absence of the atp analogue p[nh]ppa (adenos ...201323252471
the platform protein is essential for type iv pilus biogenesis.a systematic genetic analysis was performed to identify the inner membrane proteins essential for type iv pilus (t4p) expression in pseudomonas aeruginosa. by inactivating the retraction aspect of pilus function, genes essential for t4p assembly were discriminated. in contrast to previous studies in the t4p system of neisseria spp., we found that components of the inner membrane subcomplex consisting of pilmnop were not essential for surface pilus expression, whereas the highly conserved inner m ...201323413032
capture and quality control mechanisms for adenosine-5'-triphosphate binding.the catalytic events in members of the nucleotidylyl transferase superfamily are initiated by a millisecond binding of atp in the active site. through metadynamics simulations on a class i aminoacyl-trna synthetase (aarss), the largest group in the superfamily, we calculate the free energy landscape of atp selection and binding. mutagenesis studies and fluorescence spectroscopy validated the identification of the most populated intermediate states. the rapid first binding step involves formation ...201323276298
biochemical and biophysical properties of interactions between subunits of the peripheral stalk region of human v-atpase.peripheral stalk subunits of eukaryotic or mammalian vacuolar atpases (v-atpases) play key roles in regulating its assembly and disassembly. in a previous study, we purified several subunits and their isoforms of the peripheral stalk region of homo sapiens (human) v-atpase; such as c1, e1g1, h, and the n-terminal cytoplasmic region of v(o), a1. here, we investigated the in vitro binding interactions of the subunits at the stalk region and measured their specific affinities. surface plasmon reson ...201323409023
rcsb-bglj-mediated activation of cascade operon does not induce the maturation of crispr rnas in e. coli k12.prokaryotic immunity against foreign nucleic acids mediated by clustered, regularly interspaced, short palindromic repeats (crispr) depends on the expression of the crispr-associated (cas) proteins and the formation of small crispr rnas (crrnas). the crrna-loaded cas ribonucleoprotein complexes convey the specific recognition and inactivation of target nucleic acids. in e. coli k12, the maturation of crrnas and the interference with target dna is performed by the cascade complex. the transcripti ...201323392250
comparative analysis ofcas6b processing and crispr rna stability.the prokaryotic antiviral defense systems crisp r (clustered regularly interspaced short palindromic repeats)/cas (crisp rassociated) employs short crrnas (crisp r rnas) to target invading viral nucleic acids. a short spacer sequence of these crrnas can be derived from a viral genome and recognizes a reoccurring attack of a virus via base complementarity. we analyzed the effect of spacer sequences on the maturation of crrnas of the subtype i-b methanococcus maripaludis c5 crisp r cluster. the re ...201323392318
most rnas regulating ribosomal protein biosynthesis in escherichia coli are narrowly distributed to gammaproteobacteria.in escherichia coli, 12 distinct rna structures within the transcripts encoding ribosomal proteins interact with specific ribosomal proteins to allow autogenous regulation of expression from large multi-gene operons, thus coordinating ribosomal protein biosynthesis across multiple operons. however, these rna structures are typically not represented in the rna families database or annotated in genomic sequences databases, and their phylogenetic distribution is largely unknown. to investigate the ...201323396277
structure of the cmr2-cmr3 subcomplex of the cmr rna silencing complex.the cmr complex is an rna-guided effector complex that cleaves invader rna in the prokaryotic immune response mediated by the crispr (clustered regularly interspaced short palindromic repeat)-cas system. here, we report the crystal structure of a cmr subcomplex containing cmr2 (cas10) and cmr3 subunits at 2.8 å resolution. the structure revealed a dual ferredoxin fold and glycine-rich loops characteristic of previously known repeat-associated mysterious proteins and two unique insertion elements ...201323395183
dramatic structural changes resulting from the loss of a crucial hydrogen bond in the hinge region involved in c-terminal helix swapping in sure: a survival protein from salmonella typhimurium.domain swapping is an interesting feature of some oligomeric proteins in which each protomer of the oligomer provides an identical surface for exclusive interaction with a segment or domain belonging to another protomer. here we report results of mutagenesis experiments on the structure of c-terminal helix swapped dimer of a stationary phase survival protein from salmonella typhimurium (stsure). wild type stsure is a dimer in which a large helical segment at the c-terminus and a tetramerization ...201323409101
transition of a microrna from repressing to activating translation depending on the extent of base pairing with the target.micrornas are major post-transcriptional regulators of gene expression. here we show in the ancient protozoan giardia lamblia a snorna-derived 26-nucleotide microrna, mir3, which represses the translation of histone h2a mrna containing an imperfect target but enhances translation when the target is made fully complementary. a stepwise mutational analysis of the fully complementary target showed that the activating effect of mir3 was significantly reduced when a single nucleotide at the 5'-end of ...201323405193
twisting and subunit rotation in single f(o)(f1)-atp synthase.f(o)f(1)-atp synthases are ubiquitous proton- or ion-powered membrane enzymes providing atp for all kinds of cellular processes. the mechanochemistry of catalysis is driven by two rotary nanomotors coupled within the enzyme. their different step sizes have been observed by single-molecule microscopy including videomicroscopy of fluctuating nanobeads attached to single enzymes and single-molecule förster resonance energy transfer. here we review recent developments of approaches to monitor the st ...201323267178
the zebrafish mutants for the v-atpase subunits d, ac45, e, h and c and their variable pigment dilution phenotype.the v-atpase is a proton pump that creates an acidic medium, necessary for lysosome function and vesicular traffic. it is also essential for several developmental processes. many enzymes, like the v-atpase, are assemblies of multiple subunits, in which each one performs a specific function required to achieve full activity. in the zebrafish v-atpase 15 different subunits form this multimeric complex and mutations in any of these subunits induce hypopigmentation or pigment dilution phenotype. we ...201323375000
a coordinated proteomic approach for identifying proteins that interact with the e. coli ribosomal protein s12.the bacterial ribosomal protein s12 contains a universally conserved d88 residue on a loop region thought to be critically involved in translation due to its proximal location to the a site of the 30s subunit. while d88 mutants are lethal this residue has been found to be post-translationally modified to β-methylthioaspartic acid, a post-translational modification (ptm) identified in s12 orthologs from several phylogenetically distinct bacteria. in a previous report focused on characterizing thi ...201323305560
the ga-minor submotif as a case study of rna modularity, prediction, and design.complex natural rnas such as the ribosome, group i and group ii introns, and rnase p exemplify the fact that three-dimensional (3d) rna structures are highly modular and hierarchical in nature. tertiary rna folding typically takes advantage of a rather limited set of recurrent structural motifs that are responsible for controlling bends or stacks between adjacent helices. herein, the ga minor and related structural motifs are presented as a case study to highlight several structural and folding ...201323378290
take home lessons from studies of related proteins.the 'fold approach' involves a detailed analysis of the folding of several topologically, structurally and/or evolutionarily related proteins. such studies can reveal determinants of the folding mechanism beyond the gross topology, and can dissect the residues required for folding from those required for stability or function. while this approach has not yet matured to the point where we can predict the native conformation of any polypeptide chain in silico, it has been able to highlight, amongs ...201323265640
evidence for niche partitioning revealed by the distribution of sulfur oxidation genes collected from areas of a terrestrial sulfidic spring with differing geochemical conditions.the diversity and phylogenetic significance of bacterial genes in the environment has been well studied, but comparatively little attention has been devoted to understanding the functional significance of different variations of the same metabolic gene that occur in the same environment. we analyzed the geographic distribution of 16s rrna pyrosequences and soxb genes along a geochemical gradient in a terrestrial sulfidic spring to identify how different taxonomic variations of the soxb gene were ...201323220955
development of novel sugar isomerases by optimization of active sites in phosphosugar isomerases for monosaccharides.phosphosugar isomerases can catalyze the isomerization of not only phosphosugar but also of monosaccharides, suggesting that the phosphosugar isomerases can be used as sugar isomerases that do not exist in nature. determination of active-site residues of phosphosugar isomerases, including ribose-5-phosphate isomerase from clostridium difficile (cdrpi), mannose-6-phosphate isomerase from bacillus subtilis (bsmpi), and glucose-6-phosphate isomerase from pyrococcus furiosus (pfgpi), was accomplishe ...201323204422
characterization of crispr rna biogenesis and cas6 cleavage-mediated inhibition of a provirus in the haloarchaeon haloferax mediterranei.the adaptive immune system comprising crispr (clustered regularly interspaced short palindromic repeats) arrays and cas (crispr-associated) genes has been discovered in a wide range of bacteria and archaea and has recently attracted comprehensive investigations. however, the subtype i-b crispr-cas system in haloarchaea has been less characterized. here, we investigated cas6-mediated rna processing in haloferax mediterranei. the cas6 cleavage site, as well as the crispr transcription start site, ...201323243301
protein translocation across the rough endoplasmic reticulum.the rough endoplasmic reticulum is a major site of protein biosynthesis in all eukaryotic cells, serving as the entry point for the secretory pathway and as the initial integration site for the majority of cellular integral membrane proteins. the core components of the protein translocation machinery have been identified, and high-resolution structures of the targeting components and the transport channel have been obtained. research in this area is now focused on obtaining a better understandin ...201323251026
trnahis 5-methylcytidine levels increase in response to several growth arrest conditions in saccharomyces cerevisiae.trnas are highly modified, each with a unique set of modifications. several reports suggest that trnas are hypomodified or, in some cases, hypermodified under different growth conditions and in certain cancers. we previously demonstrated that yeast strains depleted of trna(his) guanylyltransferase accumulate uncharged trna(his) lacking the g(-1) residue and subsequently accumulate additional 5-methylcytidine (m(5)c) at residues c(48) and c(50) of trna(his), due to the activity of the m(5)c-methy ...201323249748
crystallization and preliminary x-ray crystallographic analyses of thermus thermophilus backtracked rna polymerase.dna-dependent rna polymerase (rnap) synthesizes rna complementary to the template dna. during transcript elongation, rnap often undergoes backward translocation ('backtracking') by dissociating the 3' end of the nascent rna transcript from the template dna. while the backtracked state of rnap is inactive in rna elongation, it actively hydrolyses the rna 3' end to regenerate the active elongation complex. to study the structural basis of the backtracked state and its cleavage activity, two backtr ...201323385762
structural and mechanistic characterization of l-histidinol phosphate phosphatase from the polymerase and histidinol phosphatase family of proteins.l-histidinol phosphate phosphatase (hpp) catalyzes the hydrolysis of l-histidinol phosphate to l-histidinol and inorganic phosphate, the penultimate step in the biosynthesis of l-histidine. hpp from the polymerase and histidinol phosphatase (php) family of proteins possesses a trinuclear active site and a distorted (β/α)(7)-barrel protein fold. this group of enzymes is closely related to the amidohydrolase superfamily of enzymes. the mechanism of phosphomonoester bond hydrolysis by the php famil ...201323327428
cloning, expression, purification, crystallization and preliminary x-ray crystallographic study of thymidylate kinase (ttha1607) from thermus thermophilus hb8.nucleotide biosynthesis plays a key role in cell survival and cell proliferation. thymidylate kinase is an enzyme that catalyses the conversion of dtmp to dtdp using atp-mg(2+) as a phosphoryl-donor group. this enzyme is present at the junction of the de novo and salvage pathways; thus, any inhibitor designed against it will result in cell death. this highlights the importance of this enzyme as a drug target. thymidylate kinase from the extremely thermophilic organism thermus thermophilus hb8 ha ...201323385749
large domain motions in ago protein controlled by the guide dna-strand seed region determine the ago-dna-mrna complex recognition process.the recognition mechanism and cleavage activity of argonaute (ago), mirna, and mrna complexes are the core processes to the small non-coding rna world. the 5' nucleation at the 'seed' region (position 2-8) of mirna was believed to play a significant role in guiding the recognition of target mrnas to the given mirna family. in this paper, we have performed all-atom molecular dynamics simulations of the related and recently revealed ago-dna:mrna ternary complexes to study the dynamics of the guide ...201323382927
conserved structural chemistry for incision activity in structurally non-homologous apurinic/apyrimidinic endonuclease ape1 and endonuclease iv dna repair enzymes.non-coding apurinic/apyrimidinic (ap) sites in dna form spontaneously and as dna base excision repair intermediates are the most common toxic and mutagenic in vivo dna lesion. for repair, ap sites must be processed by 5' ap endonucleases in initial stages of base repair. human ape1 and bacterial nfo represent the two conserved 5' ap endonuclease families in the biosphere; they both recognize ap sites and incise the phosphodiester backbone 5' to the lesion, yet they lack similar structures and me ...201323355472
rnase h2 roles in genome integrity revealed by unlinking its activities.ribonuclease h2 (rnase h2) protects genome integrity by its dual roles of resolving transcription-related r-loops and ribonucleotides incorporated in dna during replication. to unlink these two functions, we generated a saccharomyces cerevisiae rnase h2 mutant that can resolve r-loops but cannot cleave single ribonucleotides in dna. this mutant definitively correlates the 2-5 bp deletions observed in rnh201δ strains with single rnmps in dna. it also establishes a connection between r-loops and s ...201323355612
molecular paleontology: a biochemical model of the ancestral ribosome.ancient components of the ribosome, inferred from a consensus of previous work, were constructed in silico, in vitro and in vivo. the resulting model of the ancestral ribosome presented here incorporates ∼20% of the extant 23s rrna and fragments of five ribosomal proteins. we test hypotheses that ancestral rrna can: (i) assume canonical 23s rrna-like secondary structure, (ii) assume canonical tertiary structure and (iii) form native complexes with ribosomal protein fragments. footprinting experi ...201323355613
systematic functional comparative analysis of four single-stranded dna-binding proteins and their affection on viral rna metabolism.the accumulation of single-stranded dna-binding (ssb) proteins is essential for organisms and has various applications. however, no study has simultaneously and systematically compared the characteristics of ssb proteins. in addition, ssb proteins may bind rna and play an unknown biological role in rna metabolism. here, we expressed a novel species of ssb protein derived from thermococcus kodakarensis kod1 (kod), as well as ssb proteins from thermus thermophilus (tth), escherichia coli, and sulf ...201323365690
propylisopropylacetic acid (pia), a constitutional isomer of valproic acid, uncompetitively inhibits arachidonic acid acylation by rat acyl-coa synthetase 4: a potential drug for bipolar disorder.mood stabilizers used for treating bipolar disorder (bd) selectively downregulate arachidonic acid (aa) turnover (deacylation-reacylation) in brain phospholipids, when given chronically to rats. in vitro studies suggest that one of these, valproic acid (vpa), which is teratogenic, reduces aa turnover by inhibiting the brain long-chain acyl-coa synthetase (acsl)4 mediated acylation of aa to aa-coa. we tested whether non-teratogenic vpa analogues might also inhibit acsl4 catalyzed acylation, and t ...201323354024
the molecular mechanism of hsp100 chaperone inhibition by the prion curing agent guanidinium chloride.the hsp100 chaperones clpb and hsp104 utilize the energy from atp hydrolysis to reactivate aggregated proteins in concert with the dnak/hsp70 chaperone system, thereby playing an important role in protein quality control. they belong to the family of aaa+ proteins (atpases associated with various cellular activities), possess two nucleotide binding domains per monomer (nbd1 and nbd2), and oligomerize into hexameric ring complexes. furthermore, hsp104 is involved in yeast prion propagation and in ...201323341453
distinct conformation of atp molecule in solution and on protein.adenosine triphosphate (atp) is a versatile molecule used mainly for energy and a phosphate source. the hydrolysis of γ phosphate initiates the reactions and these reactions almost always start when atp binds to protein. therefore, there should be a mechanism to prevent spontaneous hydrolysis reaction and a mechanism to lead atp to a pure energy source or to a phosphate source. to address these questions, we extensively analyzed the effect of protein to atp conformation based on the sampling of ...201327493535
investigation of stable and transient protein-protein interactions: past, present, and future.this article presents an overview of the literature and a review of recent advances in the analysis of stable and transient protein-protein interactions (ppis) with a focus on their function within cells, organs, and organisms. the significance of ptms within the ppis is also discussed. we focus on methods to study ppis and methods of detecting ppis, with particular emphasis on electrophoresis-based and ms-based investigation of ppis, including specific examples. the validation of ppis is emphas ...201323193082
in vitro reconstitution of cascade-mediated crispr immunity in streptococcus thermophilus.clustered regularly interspaced short palindromic repeats (crispr)-encoded immunity in type i systems relies on the cascade (crispr-associated complex for antiviral defence) ribonucleoprotein complex, which triggers foreign dna degradation by an accessory cas3 protein. to establish the mechanism for adaptive immunity provided by the streptococcus thermophilus crispr4-cas (crispr-associated) system (st-crispr4-cas), we isolated an effector complex (st-cascade) containing 61-nucleotide crispr rna ...201323334296
regulation of argonaute slicer activity by guide rna 3' end interactions with the n-terminal lobe.structural studies indicate that binding of both the guide rna (sirna and mirna) and the target mrna trigger substantial conformational changes in the argonaute proteins. here we explore the role of the n-terminal lobe (and its paz domain) in these conformational changes using biochemical and cell culture-based approaches. in vitro, whereas deletion (or mutation) of the n-terminal lobe of dmago1 and dmago2 had no effect on binding affinity to guide rnas, we observed a loss of protection of the 3 ...201323329841
deep transcriptome-sequencing and proteome analysis of the hydrothermal vent annelid alvinella pompejana identifies the cvp-bias as a robust measure of eukaryotic thermostability.alvinella pompejana is an annelid worm that inhabits deep-sea hydrothermal vent sites in the pacific ocean. living at a depth of approximately 2500 meters, these worms experience extreme environmental conditions, including high temperature and pressure as well as high levels of sulfide and heavy metals. a. pompejana is one of the most thermotolerant metazoans, making this animal a subject of great interest for studies of eukaryotic thermoadaptation.201323324115
snapshots of a protein folding intermediate.we have investigated the folding dynamics of thermus thermophilus cytochrome c(552) by time-resolved fluorescence energy transfer between the heme and each of seven site-specific fluorescent probes. we have found both an equilibrium unfolding intermediate and a distinct refolding intermediate from kinetics studies. depending on the protein region monitored, we observed either two-state or three-state denaturation transitions. the unfolding intermediate associated with three-state folding exhibit ...201323319660
structural characterization of a mouse ortholog of human neil3 with a marked preference for single-stranded dna.endonuclease viii-like 3 (neil3) is a dna glycosylase of the base excision repair pathway that protects cells from oxidative dna damage by excising a broad spectrum of cytotoxic and mutagenic base lesions. interestingly, neil3 exhibits an unusual preference for dna with single-stranded regions. here, we report the 2.0 å crystal structure of a neil3 enzyme. although the glycosylase region of mouse neil3 (mmuneil3δ324) exhibits the same overall fold as that of other fpg/nei proteins, it presents d ...201323313161
the remorin c-terminal anchor was shaped by convergent evolution among membrane binding domains.strem1.3 remorin is a well-established plant raftophilic protein, predominantly associated with sterol- and sphingolipid-rich membrane rafts. we recently identified a c-terminal domain (remca) required and sufficient for strem1.3 anchoring to the plasma membrane. here, we report a search for homologs and analogs of remca domain in publicly available protein sequence and structure databases. we could not identify remca homologous domains outside the remorin family but we identified domains sharin ...201323299327
characterization and genomic analysis of kraft lignin biodegradation by the beta-proteobacterium cupriavidus basilensis b-8. 201323298573
the n termini of a-subunit isoforms are involved in signaling between vacuolar h+-atpase (v-atpase) and cytohesin-2.previously, we reported an acidification-dependent interaction of the endosomal vacuolar h(+)-atpase (v-atpase) with cytohesin-2, a gdp/gtp exchange factor (gef), suggesting that it functions as a ph-sensing receptor. here, we have studied the molecular mechanism of signaling between the v-atpase, cytohesin-2, and arf gtp-binding proteins. we found that part of the n-terminal cytosolic tail of the v-atpase a2-subunit (a2n), corresponding to its first 17 amino acids (a2n(1-17)), potently modulate ...201323288846
methylerythritol phosphate pathway of isoprenoid biosynthesis.isoprenoids are a class of natural products with more than 55,000 members. all isoprenoids are constructed from two precursors, isopentenyl diphosphate and its isomer dimethylallyl diphosphate. two of the most important discoveries in isoprenoid biosynthetic studies in recent years are the elucidation of a second isoprenoid biosynthetic pathway [the methylerythritol phosphate (mep) pathway] and a modified mevalonic acid (mva) pathway. in this review, we summarize mechanistic insights on the mep ...201323746261
coaggregation occurs amongst bacteria within and between biofilms in domestic showerheads.showerheads support the development of multi-species biofilms that can be unsightly, produce malodor, and may harbor pathogens. the outer-surface spray-plates of many showerheads support visible biofilms that likely contain a mixture of bacteria from freshwater and potentially from human users. coaggregation, a mechanism by which genetically distinct bacteria specifically recognize one another, may contribute to the retention and enrichment of different species within these biofilms. the aim of ...201323194413
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