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structure and function of hiv-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition.the rapid replication of hiv-1 and the errors made during viral replication cause the virus to evolve rapidly in patients, making the problems of vaccine development and drug therapy particularly challenging. in the absence of an effective vaccine, drugs are the only useful treatment. anti-hiv drugs work; so far drug therapy has saved more than three million years of life. unfortunately, hiv-1 develops resistance to all of the available drugs. although a number of useful anti-hiv drugs have been ...200919022262
recognition of aminoacyl-trna: a common molecular mechanism revealed by cryo-em.the accuracy of ribosomal translation is achieved by an initial selection and a proofreading step, mediated by ef-tu, which forms a ternary complex with aminoacyl(aa)-trna. to study the binding modes of different aa-trnas, we compared cryo-em maps of the kirromycin-stalled ribosome bound with ternary complexes containing phe-trna(phe), trp-trna(trp), or leu-trna(leui). the three maps suggest a common binding manner of cognate aa-trnas in their specific binding with both the ribosome and ef-tu. a ...200819020518
phylogenetic analysis of rubella virus strains from an outbreak in madrid, spain, from 2004 to 2005.an outbreak of rubella affected 460 individuals in 2004 and 2005 in the community of madrid, spain. most of the patients were nonvaccinated latin american immigrants or spanish males. this study presents the first data on rubella virus genotypes in spain. forty selected clinical samples (2 urine, 5 serum, 3 blood, 2 saliva, and 28 pharyngeal exudate samples) from 40 cases were collected. the 739-nucleotide sequence recommended by the world health organization obtained from viral rna in these sam ...200919020066
phylogenetic analysis of rubella virus strains from an outbreak in madrid, spain, from 2004 to 2005.an outbreak of rubella affected 460 individuals in 2004 and 2005 in the community of madrid, spain. most of the patients were nonvaccinated latin american immigrants or spanish males. this study presents the first data on rubella virus genotypes in spain. forty selected clinical samples (2 urine, 5 serum, 3 blood, 2 saliva, and 28 pharyngeal exudate samples) from 40 cases were collected. the 739-nucleotide sequence recommended by the world health organization obtained from viral rna in these sam ...200919020066
genome-wide survey of prokaryotic serine proteases: analysis of distribution and domain architectures of five serine protease families in prokaryotes.serine proteases are one of the most abundant groups of proteolytic enzymes found in all the kingdoms of life. while studies have established significant roles for many prokaryotic serine proteases in several physiological processes, such as those associated with metabolism, cell signalling, defense response and development, functional associations for a large number of prokaryotic serine proteases are relatively unknown. current analysis is aimed at understanding the distribution and probable b ...200819019219
novel escherichia coli rf1 mutants with decreased translation termination activity and increased sensitivity to the cytotoxic effect of the bacterial toxins kid and rele.novel mutations in prfa, the gene for the polypeptide release factor rf1 of escherichia coli, were isolated using a positive genetic screen based on the pard (kis, kid) toxin-antitoxin system. this original approach allowed the direct selection of mutants with altered translational termination efficiency at uag codons. the isolated prfa mutants displayed a approximately 10-fold decrease in uag termination efficiency with no significant changes in rf1 stability in vivo. all three mutations, g121s ...200919019162
recr-mediated modulation of recf dimer specificity for single- and double-stranded dna.recf pathway proteins play an important role in the restart of stalled replication and dna repair in prokaryotes. following dna damage, recf, recr, and reco initiate homologous recombination (hr) by loading of the reca recombinase on single-stranded (ss) dna, protected by ssdna-binding protein. the specific role of recf in this process is not well understood. previous studies have proposed that recf directs the recor complex to boundaries of damaged dna regions by recognizing single-stranded/dou ...200919017635
transposition of an insertion sequence, istth7, in the genome of the extreme thermophile thermus thermophilus hb8.we have identified an active insertion sequence (is) in the genome of thermus thermophilus hb8. transposition was detected as insertional inactivation of a 16s rrna methyltransferase gene, rsmg, resulting in streptomycin resistance. the is element, istth7, is 1029 bp in length, encodes an imperfect 12 bp inverted repeat, and produces a 9 bp direct repeat of the target sequence. the sequence of a putative transposase encoded by istth7 indicates that it is a member of the is427 group within the is ...200819016874
probing protein structure by amino acid-specific covalent labeling and mass spectrometry.for many years, amino acid-specific covalent labeling has been a valuable tool to study protein structure and protein interactions, especially for systems that are difficult to study by other means. these covalent labeling methods typically map protein structure and interactions by measuring the differential reactivity of amino acid side chains. the reactivity of amino acids in proteins generally depends on the accessibility of the side chain to the reagent, the inherent reactivity of the label ...200919016300
revisiting the mechanism of macrolide-antibiotic resistance mediated by ribosomal protein l22.bacterial antibiotic resistance can occur by many mechanisms. an intriguing class of mutants is resistant to macrolide antibiotics even though these drugs still bind to their targets. for example, a 3-residue deletion (deltamkr) in ribosomal protein l22 distorts a loop that forms a constriction in the ribosome exit tunnel, apparently allowing nascent-chain egress and translation in the presence of bound macrolides. here, however, we demonstrate that deltamkr and wild-type ribosomes show comparab ...200819015512
structural and biochemical studies of tigar (tp53-induced glycolysis and apoptosis regulator).activation of the p53 tumor suppressor by cellular stress leads to variable responses ranging from growth inhibition to apoptosis. tigar is a novel p53-inducible gene that inhibits glycolysis by reducing cellular levels of fructose-2,6-bisphosphate, an activator of glycolysis and inhibitor of gluconeogenesis. here we describe structural and biochemical studies of tigar from danio rerio. the overall structure forms a histidine phosphatase fold with a phosphate molecule coordinated to the catalyti ...200919015259
contributions of the two accessory subunits, rnaseh2b and rnaseh2c, to the activity and properties of the human rnase h2 complex.eukaryotic rnase h2 is a heterotrimeric enzyme. here, we show that the biochemical composition and stoichiometry of the human rnase h2 complex is consistent with the properties previously deduced from genetic studies. the catalytic subunit of eukaryotic rnase h2, rnaseh2a, is well conserved and similar to the monomeric prokaryotic rnase hii. in contrast, the rnaseh2b and rnaseh2c subunits from human and saccharomyces cerevisiae share very little homology, although they both form soluble b/c comp ...200919015152
contributions of the two accessory subunits, rnaseh2b and rnaseh2c, to the activity and properties of the human rnase h2 complex.eukaryotic rnase h2 is a heterotrimeric enzyme. here, we show that the biochemical composition and stoichiometry of the human rnase h2 complex is consistent with the properties previously deduced from genetic studies. the catalytic subunit of eukaryotic rnase h2, rnaseh2a, is well conserved and similar to the monomeric prokaryotic rnase hii. in contrast, the rnaseh2b and rnaseh2c subunits from human and saccharomyces cerevisiae share very little homology, although they both form soluble b/c comp ...200919015152
prevalence of pfmdr1, pfcrt, pfdhfr and pfdhps mutations associated with drug resistance, in luanda, angola.malaria is the infectious disease causing the highest morbidity and mortality in angola and due to widespread chloroquine (cq) resistance, the country has recently changed its first-line treatment recommendations for uncomplicated malaria, from cq to artemisinin combination therapies (act) in adults, and sulphadoxine/pyrimethamine (s/p) in pregnant women. loss of sp sensitivity is, however, progressing rapidly in africa and, in this study, were investigated a number of molecular markers associat ...200819014684
a short-oligonucleotide microarray that allows improved detection of gastrointestinal tract microbial communities.the human gastrointestinal (gi) tract contains a diverse collection of bacteria, most of which are unculturable by conventional microbiological methods. increasingly molecular profiling techniques are being employed to examine this complex microbial community. the purpose of this study was to develop a microarray technique based on 16s ribosomal gene sequences for rapidly monitoring the microbial population of the gi tract.200819014434
probing the paracoccus denitrificans cytochrome c(1)-cytochrome c(552) interaction by mutagenesis and fast kinetics.electron transfer (et) between paracoccus denitrificans cytochrome (cyt) c(1) and cytochrome c(552) was studied using the soluble redox fragments cyt c(1cf) and cyt c(552f). a new ruthenium cyt c(552f) derivative labeled at c23 (ru(z)-23-c(552f)) was designed to measure rapid electron transfer with cyt c(1cf) in the physiological direction using flash photolysis. the bimolecular rate constant k(12) decreased rapidly with ionic strength above 40 mm, consistent with a diffusional process guided by ...200819006325
high tolerance for ionizable residues in the hydrophobic interior of proteins.internal ionizable groups are quite rare in water-soluble globular proteins. presumably, this reflects the incompatibility between charges and the hydrophobic environment in the protein interior. here we show that proteins can have an inherently high tolerance for internal ionizable groups. the 25 internal positions in staphylococcal nuclease were substituted one at a time with lys, glu, or asp without abolishing enzymatic activity and without detectable changes in the conformation of the protei ...200819004768
collective dynamics of the ribosomal tunnel revealed by elastic network modeling.the collective dynamics of the nascent polypeptide exit tunnel are investigated with the computationally efficient elastic network model using normal mode analysis. the calculated normal modes are considered individually and in linear combinations with different coefficients mimicking the phase angles between modes, in order to follow the mechanistic motions of tunnel wall residues. the low frequency fluctuations indicate three distinct regions along the tunnel-the entrance, the neck, and the ex ...200919004020
the hsp70 chaperone system maintains high concentrations of active proteins and suppresses atp consumption during heat shock.hsp70 chaperones assist protein folding by cycling between the atp-bound t state with low affinity for substrates and the adp-bound r state with high affinity for substrates. the transition from the t to r state is catalyzed by the synergistic action of the substrate and dnaj cochaperones. the reverse transition from the r state to the t state is accelerated by the nucleotide exchange factor grpe. these two processes, t-to-r and r-to-t conversion, are affected differently by temperature change. ...200719003436
escherichia coli tmrna lacking pseudoknot 1 tags truncated proteins in vivo and in vitro.transfer-messenger rna (tmrna) and protein smpb facilitate trans-translation, a quality-control process that tags truncated proteins with short peptides recognized by a number of proteases and recycles ribosomes stalled at the 3' end of mrna templates lacking stop codons. the tmrna molecule is a hybrid of trna- and mrna-like domains that are usually connected by four pseudoknots (pk1-pk4). replacement of pk1 with a single-stranded rna yields pk1l, a mutant tmrna that tags truncated proteins very ...200919001120
core structure of the yeast spt4-spt5 complex: a conserved module for regulation of transcription elongation.the spt4-spt5 complex is an essential rna polymerase ii elongation factor found in all eukaryotes and important for gene regulation. we report here the crystal structure of saccharomyces cerevisiae spt4 bound to the ngn domain of spt5. this structure reveals that spt4-spt5 binding is governed by an acid-dipole interaction between spt5 and spt4. mutations that disrupt this interaction disrupt the complex. residues forming this pivotal interaction are conserved in the archaeal homologs of spt4 and ...200819000817
rv0802c from mycobacterium tuberculosis: the first structure of a succinyltransferase with the gnat fold.gene rv0802c from mycobacterium tuberculosis encodes a 218-amino-acid protein and is annotated as a hypothetical protein with homology to gcn5-related n-acetyltransferases. the structure of rv0802c was determined in an unliganded form to 2.0 a resolution utilizing single-wavelength anomalous dispersion from a samarium soak that resulted in a single bound sm(3+):citrate(2) complex. the structure confirms that rv0802c exhibits the gcn5-related n-acetyltransferase fold and revealed a tetramer compo ...200818997321
organization of an activator-bound rna polymerase holoenzyme.transcription initiation involves the conversion from closed promoter complexes, comprising rna polymerase (rnap) and double-stranded promoter dna, to open complexes, in which the enzyme is able to access the dna template in a single-stranded form. the complex between bacterial rnap and its major variant sigma factor sigma(54) remains as a closed complex until atp hydrolysis-dependent remodeling by activator proteins occurs. this remodeling facilitates dna melting and allows the transition to th ...200818995832
insights into translational termination from the structure of rf2 bound to the ribosome.the termination of protein synthesis occurs through the specific recognition of a stop codon in the a site of the ribosome by a release factor (rf), which then catalyzes the hydrolysis of the nascent protein chain from the p-site transfer rna. here we present, at a resolution of 3.5 angstroms, the crystal structure of rf2 in complex with its cognate uga stop codon in the 70s ribosome. the structure provides insight into how rf2 specifically recognizes the stop codon; it also suggests a model for ...200818988853
recognition of a common rdna target site in archaea and eukarya by analogous laglidadg and his-cys box homing endonucleases.the presence of a homing endonuclease gene (heg) within a microbial intron or intein empowers the entire element with the ability to invade genomic targets. the persistence of a homing endonuclease lineage depends in part on conservation of its dna target site. one such rdna sequence has been invaded both in archaea and in eukarya, by laglidadg and his-cys box homing endonucleases, respectively. the bases encoded by this target include a universally conserved ribosomal structure, termed helix 69 ...200818984620
unfolding thermodynamics of the delta-domain in the prohead i subunit of phage hk97: determination by factor analysis of raman spectra.an early step in the morphogenesis of the double-stranded dna (dsdna) bacteriophage hk97 is the assembly of a precursor shell (prohead i) from 420 copies of a 384-residue subunit (gp5). although formation of prohead i requires direct participation of gp5 residues 2-103 (delta-domain), this domain is eliminated by viral protease prior to subsequent shell maturation and dna packaging. the prohead i delta-domain is thought to resemble a phage scaffolding protein, by virtue of its highly alpha-helic ...200918983851
unfolding thermodynamics of the delta-domain in the prohead i subunit of phage hk97: determination by factor analysis of raman spectra.an early step in the morphogenesis of the double-stranded dna (dsdna) bacteriophage hk97 is the assembly of a precursor shell (prohead i) from 420 copies of a 384-residue subunit (gp5). although formation of prohead i requires direct participation of gp5 residues 2-103 (delta-domain), this domain is eliminated by viral protease prior to subsequent shell maturation and dna packaging. the prohead i delta-domain is thought to resemble a phage scaffolding protein, by virtue of its highly alpha-helic ...200918983851
bacterial heme-transport proteins and their heme-coordination modes.efficient iron acquisition is critical for an invading microbe's survival and virulence. most of the iron in mammals is incorporated into heme, which can be plundered by certain bacterial pathogens as a nutritional iron source. utilization of exogenous heme by bacteria involves the binding of heme or hemoproteins to the cell surface receptors, followed by the transport of heme into cells. once taken into the cytosol, heme is presented to heme oxygenases where the tetrapyrrole ring is cleaved in ...200818977196
bacterial heme-transport proteins and their heme-coordination modes.efficient iron acquisition is critical for an invading microbe's survival and virulence. most of the iron in mammals is incorporated into heme, which can be plundered by certain bacterial pathogens as a nutritional iron source. utilization of exogenous heme by bacteria involves the binding of heme or hemoproteins to the cell surface receptors, followed by the transport of heme into cells. once taken into the cytosol, heme is presented to heme oxygenases where the tetrapyrrole ring is cleaved in ...200818977196
translation initiation factor if1 of bacillus stearothermophilus and thermus thermophilus substitute for escherichia coli if1 in vivo and in vitro without a direct if1-if2 interaction.bacterial translation initiation factor if1 is homologous to archaeal aif1a and eukaryal eif1a, which form a complex with their homologous if2-like factors (aif5b and eif5b respectively) during initiation of protein synthesis. a similar if1-if2 interaction is assumed to occur in all bacteria and supported by cross-linking data and stabilization of the 30s-if2 interaction by if1. here we compare escherichia coli if1 with thermophilic factors from bacillus stearothermophilus and thermus thermophil ...200818976282
cytochrome c oxidase: exciting progress and remaining mysteries.cytochrome c oxidase generates a proton motive force by two separate mechanisms. the first mechanism is similar to that postulated by peter mitchell, and is based on electrons and protons used to generate water coming from opposite sides of the membrane. the second mechanism was not initially anticipated, but is now firmly established as a proton pump. a brief review of the current state of our understanding of the proton pump of cytochrome oxidase is presented. we have come a long way since the ...200818975062
sequence and structural evolution of the ksga/dim1 methyltransferase family.one of the 60 or so genes conserved in all domains of life is the ksga/dim1 orthologous group. enzymes from this family perform the same post-transcriptional nucleotide modification in ribosome biogenesis, irrespective of organism. despite this common function, divergence has enabled some family members to adopt new and sometimes radically different functions. for example, in s. cerevisiae dim1 performs two distinct functions in ribosome biogenesis, while human mttfb is not only an rrna methyltr ...200818959795
automated motif extraction and classification in rna tertiary structures.we used a novel graph-based approach to extract rna tertiary motifs. we cataloged them all and clustered them using an innovative graph similarity measure. we applied our method to three widely studied structures: haloarcula marismortui 50s (h.m 50s), escherichia coli 50s (e. coli 50s), and thermus thermophilus 16s (t.th 16s) rnas. we identified 10 known motifs without any prior knowledge of their shapes or positions. we additionally identified four putative new motifs.200818957493
rna in motion.although rna duplex regions are highly structured and inflexible, other elements of an rna molecule are capable of dynamic motions. these flexible regions are the sites of interactions with small molecules, proteins, and other rnas, yet there are few descriptions of these regions that include the timescale and amplitude of their motions. no one technique is sufficient to accurately describe these motions, but the combination of in vitro methods, particularly nmr relaxation methods, and more robu ...200818957331
the rna polymerase "switch region" is a target for inhibitors.the alpha-pyrone antibiotic myxopyronin (myx) inhibits bacterial rna polymerase (rnap). here, through a combination of genetic, biochemical, and structural approaches, we show that myx interacts with the rnap "switch region"--the hinge that mediates opening and closing of the rnap active center cleft--to prevent interaction of rnap with promoter dna. we define the contacts between myx and rnap and the effects of myx on rnap conformation and propose that myx functions by interfering with opening ...200818957204
the p. furiosus mre11/rad50 complex promotes 5' strand resection at a dna double-strand break.the mre11/rad50 complex has been implicated in the early steps of dna double-strand break (dsb) repair through homologous recombination in several organisms. however, the enzymatic properties of this complex are incompatible with the generation of 3' single-stranded dna for recombinase loading and strand exchange. in thermophilic archaea, the mre11 and rad50 genes cluster in an operon with genes encoding a helicase, hera, and a 5' to 3' exonuclease, nura, suggesting a common function. here we sh ...200818957200
tie me up, tie me down: inhibiting rna polymerase.mechanistic understanding of antibiotic action can yield crucial insights that aid in the design of new antibiotics. in this issue, mukhopadhyay et al. (2008) uncover the mechanism by which the antibiotic myxopyronin inhibits bacterial rna polymerase, suggesting a new target region in rna polymerase for inhibitor design.200818957193
structure of the yeast vacuolar atpase.the subunit architecture of the yeast vacuolar atpase (v-atpase) was analyzed by single particle transmission electron microscopy and electrospray ionization (esi) tandem mass spectrometry. a three-dimensional model of the intact v-atpase was calculated from two-dimensional projections of the complex at a resolution of 25 angstroms. images of yeast v-atpase decorated with monoclonal antibodies against subunits a, e, and g position subunit a within the pseudo-hexagonal arrangement in the v1, the ...200818955482
genomics of bacteria and archaea: the emerging dynamic view of the prokaryotic world.the first bacterial genome was sequenced in 1995, and the first archaeal genome in 1996. soon after these breakthroughs, an exponential rate of genome sequencing was established, with a doubling time of approximately 20 months for bacteria and approximately 34 months for archaea. comparative analysis of the hundreds of sequenced bacterial and dozens of archaeal genomes leads to several generalizations on the principles of genome organization and evolution. a crucial finding that enables function ...200818948295
comparing the xylose reductase/xylitol dehydrogenase and xylose isomerase pathways in arabinose and xylose fermenting saccharomyces cerevisiae strains.ethanolic fermentation of lignocellulosic biomass is a sustainable option for the production of bioethanol. this process would greatly benefit from recombinant saccharomyces cerevisiae strains also able to ferment, besides the hexose sugar fraction, the pentose sugars, arabinose and xylose. different pathways can be introduced in s. cerevisiae to provide arabinose and xylose utilisation. in this study, the bacterial arabinose isomerase pathway was combined with two different xylose utilisation p ...200818947407
transcription inactivation through local refolding of the rna polymerase structure.structural studies of antibiotics not only provide a shortcut to medicine allowing for rational structure-based drug design, but may also capture snapshots of dynamic intermediates that become 'frozen' after inhibitor binding. myxopyronin inhibits bacterial rna polymerase (rnap) by an unknown mechanism. here we report the structure of dmyx--a desmethyl derivative of myxopyronin b--complexed with a thermus thermophilus rnap holoenzyme. the antibiotic binds to a pocket deep inside the rnap clamp h ...200918946472
side-chain recognition and gating in the ribosome exit tunnel.the ribosome is a large complex catalyst responsible for the synthesis of new proteins, an essential function for life. new proteins emerge from the ribosome through an exit tunnel as nascent polypeptide chains. recent findings indicate that tunnel interactions with the nascent polypeptide chain might be relevant for the regulation of translation. however, the specific ribosomal structural features that mediate this process are unknown. performing molecular dynamics simulations, we are studying ...200818946046
higher-order association states of cellular erbb3 probed with photo-cross-linkable aptamers.nucleic acid aptamers are rapidly gaining prominence as diagnostic tools, targeting reagents, and potential therapeutics. to extend the use of aptamers into the biochemical analysis of protein interactions on the surface of live cells, we converted an enzymatically generated rna aptamer into a photo-cross-linkable affinity tag through the replacement of all uracils with 4-thiouracil. specifically, we converted a previously selected, inhibitory aptamer that binds the soluble extracellular domains ...200818942860
ruva and ruvb mutants specifically impaired for replication fork reversal.replication fork reversal (rfr) is a reaction that takes place in escherichia coli at replication forks arrested by the inactivation of a replication protein. fork reversal involves the annealing of the leading and lagging strand ends; it results in the formation of a holliday junction adjacent to dna double-strand end, both of which are processed by recombination enzymes. in several replication mutants, replication fork reversal is catalysed by the ruvab complex, originally characterized for it ...200818942176
glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia.the glycine cleavage system catalyzes the following reversible reaction: glycine + h(4)folate + nad(+) <==> 5,10-methylene-h(4)folate + co(2) + nh(3) + nadh + h(+)the glycine cleavage system is widely distributed in animals, plants and bacteria and consists of three intrinsic and one common components: those are i) p-protein, a pyridoxal phosphate-containing protein, ii) t-protein, a protein required for the tetrahydrofolate-dependent reaction, iii) h-protein, a protein that carries the aminomet ...200818941301
structural basis for specific, high-affinity tetracycline binding by an in vitro evolved aptamer and artificial riboswitch.the tetracycline aptamer is an in vitro selected rna that binds to the antibiotic with the highest known affinity of an artificial rna for a small molecule (kd approximately 0.8 nm). it is one of few aptamers known to be capable of modulating gene expression in vivo. the 2.2 a resolution cocrystal structure of the aptamer reveals a pseudoknot-like fold formed by tertiary interactions between an 11 nucleotide loop and the minor groove of an irregular helix. tetracycline binds within this interfac ...200818940672
a full-length group 1 bacterial sigma factor adopts a compact structure incompatible with dna binding.the sigma factors are the key regulators of bacterial transcription initiation. through direct read-out of promoter dna sequence, they recruit the core rna polymerase to sites of initiation, thereby dictating the rna polymerase promoter-specificity. the group 1 sigma factors, which direct the vast majority of transcription initiation during log phase growth and are essential for viability, are autoregulated by an n-terminal sequence known as sigma1.1. we report the solution structure of thermoto ...200818940669
ssb as an organizer/mobilizer of genome maintenance complexes.when duplex dna is altered in almost any way (replicated, recombined, or repaired), single strands of dna are usually intermediates, and single-stranded dna binding (ssb) proteins are present. these proteins have often been described as inert, protective dna coatings. continuing research is demonstrating a far more complex role of ssb that includes the organization and/or mobilization of all aspects of dna metabolism. escherichia coli ssb is now known to interact with at least 14 other proteins ...200818937104
path of nascent polypeptide in exit tunnel revealed by molecular dynamics simulation of ribosome.molecular dynamics simulations were carried out on thermus thermophilus 70s ribosome with and without a nascent polypeptide inside the exit tunnel. modeling of the polypeptide in the tunnel revealed two possible paths: one over arg92 of l22 and one under (from the viewpoint of 50s on top of 30s). a strong interaction between l4 and arg92 was observed without the polypeptide and when it passed over arg92. however, when the polypeptide passed under, arg92 repositioned to interact with ade2059 of 2 ...200818936244
rna folding and ribosome assembly.ribosome synthesis is a tightly regulated process that is crucial for cell survival. chemical footprinting, mass spectrometry, and cryo-electron microscopy are revealing how these complex cellular machines are assembled. rapid folding of the rrna provides a platform for protein-induced assembly of the bacterial 30s ribosome. multiple assembly pathways increase the flexibility of the assembly process, while accessory factors and modification enzymes chaperone the late stages of assembly and contr ...200818935976
three crystal forms of the bifunctional enzyme proline utilization a (puta) from bradyrhizobium japonicum.proline utilization a proteins (putas) are large (1000-1300 residues) membrane-associated bifunctional flavoenzymes that catalyze the two-step oxidation of proline to glutamate by the sequential action of proline dehydrogenase and delta(1)-pyrroline-5-carboxylate dehydrogenase domains. here, the first successful crystallization efforts for a puta protein are described. three crystal forms of puta from bradyrhizobium japonicum are reported: apparent tetragonal, hexagonal and centered monoclinic. ...200818931443
purification, crystallization and preliminary x-ray diffraction analysis of the cbs-domain pair from the methanococcus jannaschii protein mj0100.cbs domains are small protein motifs consisting of a three-stranded beta-sheet and two alpha-helices that are present in proteins of all kingdoms of life and in proteins with completely different functions. several genetic diseases in humans have been associated with mutations in their sequence, which has made them promising targets for rational drug design. the c-terminal domain of the methanococcus jannaschii protein mj0100 includes a cbs-domain pair and has been overexpressed, purified and cr ...200818931440
toward a chemical mechanism of proton pumping by the b-type cytochrome c oxidases: application of density functional theory to cytochrome ba3 of thermus thermophilus.a mechanism for proton pumping by the b-type cytochrome c oxidases is presented in which one proton is pumped in conjunction with the weakly exergonic, two-electron reduction of fe-bound o 2 to the fe-cu bridging peroxodianion and three protons are pumped in conjunction with the highly exergonic, two-electron reduction of fe(iii)- (-)o-o (-)-cu(ii) to form water and the active oxidized enzyme, fe(iii)- (-)oh,cu(ii). the scheme is based on the active-site structure of cytochrome ba 3 from thermus ...200818928258
the unique nature of mg2+ channels.considering the biological abundance and importance of mg2+, there is a surprising lack of information regarding the proteins that transport mg2+, the mechanisms by which they do so, and their physiological roles within the cell. the best characterized mg2+ channel to date is the bacterial protein cora, present in a wide range of bacterial species. the cora homolog mrs2 forms the mitochondrial mg2+ channel in all eukaryotes. physiologically, cora is involved in bacterial pathogenesis, and the mr ...200818927203
rare codons cluster.most amino acids are encoded by more than one codon. these synonymous codons are not used with equal frequency: in every organism, some codons are used more commonly, while others are more rare. though the encoded protein sequence is identical, selective pressures favor more common codons for enhanced translation speed and fidelity. however, rare codons persist, presumably due to neutral drift. here, we determine whether other, unknown factors, beyond neutral drift, affect the selection and/or d ...200818923675
conformational transition of sec machinery inferred from bacterial secye structures.over 30% of proteins are secreted across or integrated into membranes. their newly synthesized forms contain either cleavable signal sequences or non-cleavable membrane anchor sequences, which direct them to the evolutionarily conserved sec translocon (secyeg in prokaryotes and sec61, comprising alpha-, gamma- and beta-subunits, in eukaryotes). the translocon then functions as a protein-conducting channel. these processes of protein localization occur either at or after translation. in bacteria, ...200818923527
the bet v 1 fold: an ancient, versatile scaffold for binding of large, hydrophobic ligands.the major birch pollen allergen, bet v 1, is a member of the ubiquitous pr-10 family of plant pathogenesis-related proteins. in recent years, a number of diverse plant proteins with low sequence similarity to bet v 1 was identified. in addition, determination of the bet v 1 structure revealed the existence of a large superfamily of structurally related proteins. in this study, we aimed to identify and classify all bet v 1-related structures from the protein data bank and all bet v 1-related sequ ...200818922149
dna polymerases and aminoacyl-trna synthetases: shared mechanisms for ensuring the fidelity of gene expression.dna polymerases and aminoacyl-trna synthetases (arss) represent large enzyme families with critical roles in the transformation of genetic information from dna to rna to protein. dna polymerases carry out replication and collaborate in the repair of the genome, while arss provide aminoacylated trna precursors for protein synthesis. enzymes of both families face the common challenge of selecting their cognate small molecule substrates from a pool of chemically related molecules, achieving high le ...200818850722
the high-resolution nmr structure of the early folding intermediate of the thermus thermophilus ribonuclease h.elucidation of the high-resolution structures of folding intermediates is a necessary but difficult step toward the ultimate understanding of the mechanism of protein folding. here, using hydrogen-exchange-directed protein engineering, we populated the folding intermediate of the thermus thermophilus ribonuclease h, which forms before the rate-limiting transition state, by removing the unfolded regions of the intermediate, including an alpha-helix and two beta-strands (51 folded residues). using ...200818848567
proton-dependent electron transfer from cua to heme a and altered epr spectra in mutants close to heme a of cytochrome oxidase.eukaryotic cytochrome c oxidase (cco) and homologous prokaryotic forms of rhodobacter and paraccocus differ in the epr spectrum of heme a. it was noted that a histidine ligand of heme a (h102) is hydrogen bonded to serine in rhodobacter (s44) and paraccocus ccos, in contrast to glycine in the bovine enzyme. mutation of s44 to glycine shifts the heme a epr signal from g(z) = 2.82 to 2.86, closer to bovine heme a at 3.03, without modifying other properties. mutation to aspartate, however, results ...200818847227
rnomics and modomics in the halophilic archaea haloferax volcanii: identification of rna modification genes.naturally occurring rnas contain numerous enzymatically altered nucleosides. differences in rna populations (rnomics) and pattern of rna modifications (modomics) depends on the organism analyzed and are two of the criteria that distinguish the three kingdoms of life. if the genomic sequences of the rna molecules can be derived from whole genome sequence information, the modification profile cannot and requires or direct sequencing of the rnas or predictive methods base on the presence or absence ...200818844986
conformationally gated metal uptake by apomanganese superoxide dismutase.metal uptake by apomanganese superoxide dismutase in vitro is a complex process exhibiting multiphase "gated" reaction kinetics and a striking sigmoidal temperature profile that has led to a model of conformationally gated metal binding, requiring conversion between "closed" and "open" forms. this work systematically explores the structural determinants of metal binding in both wild-type (wt) apoprotein and mutational variants as a test of mechanistic models. the ph dependence of metalation unde ...200818841998
the higher level of organization of the oxidative phosphorylation system: mitochondrial supercomplexes.the organization of the oxidative phosphorylation (oxphos) system within the inner mitochondrial membrane appears to be far more complicated than previously thought. in particular, the individual protein complexes of the oxphos system (complexes i to v) were found to specifically interact forming defined supramolecular structures. blue-native polyacrylamide gel electrophoresis and single particle electron microscopy proved to be especially valuable in studying the so-called "respiratory supercom ...200818839290
crystal structure of muts2 endonuclease domain and the mechanism of homologous recombination suppression.dna recombination events need to be strictly regulated, because an increase in the recombinational frequency causes unfavorable alteration of genetic information. recent studies revealed the existence of a novel anti-recombination enzyme, muts2. however, the mechanism by which muts2 inhibits homologous recombination has been unknown. previously, we found that thermus thermophilus muts2 (ttmuts2) harbors an endonuclease activity and that this activity is confined to the c-terminal domain, whose a ...200818838375
the pretranslocation ribosome is targeted by gtp-bound ef-g in partially activated form.translocation of the trna x mrna complex through the bacterial ribosome is driven by the multidomain guanosine triphosphatase elongation factor g (ef-g). we have used isothermal titration calorimetry to characterize the binding of gdp and gtp to free ef-g at 4 degrees c, 20 degrees c, and 37 degrees c. the binding affinity of ef-g is higher to gdp than to gtp at 4 degrees c, but lower at 37 degrees c. the binding enthalpy and entropy change little with temperature in the case of gdp binding but ...200818836081
a unique combination of genetic systems for the synthesis of trehalose in rubrobacter xylanophilus: properties of a rare actinobacterial tret.trehalose is the primary organic solute in rubrobacter xylanophilus under all conditions tested, including those for optimal growth. we detected genes of four different pathways for trehalose synthesis in the genome of this organism, namely, the trehalose-6-phosphate synthase (tps)/trehalose-6-phosphate phosphatase (tpp), tres, trey/trez, and tret pathways. moreover, r. xylanophilus is the only known member of the phylum actinobacteria to harbor tret. the tps sequence is typically bacterial, but ...200818835983
structure of a sigma28-regulated nonflagellar virulence protein from campylobacter jejuni.campylobacter jejuni, a gram-negative motile bacterium, is a leading cause of human gastrointestinal infections. although the mechanism of c.jejuni-mediated enteritis appears to be multifactorial, flagella play complex roles in the virulence of this human pathogen. cj0977 is a recently identified virulence factor in c. jejuni and is expressed by a sigma(28) promoter that controls late genes in the flagellar regulon. a cj0977 mutant strain is fully motile but significantly reduced in the invasion ...200818835274
ribosomal protein l3 functions as a 'rocker switch' to aid in coordinating of large subunit-associated functions in eukaryotes and archaea.although ribosomal rnas (rrnas) comprise the bulk of the ribosome and carry out its main functions, ribosomal proteins also appear to play important structural and functional roles. many ribosomal proteins contain long, nonglobular domains that extend deep into the rrna cores. in eukaryotes and archaea, ribosomal protein l3 contains two such extended domains tethered to a common globular hub, thus providing an excellent model to address basic questions relating to ribosomal protein structure/fun ...200818832371
the mycoplasma pneumoniae mpn229 gene encodes a protein that selectively binds single-stranded dna and stimulates recombinase a-mediated dna strand exchange.mycoplasma pneumoniae has previously been characterized as a micro-organism that is genetically highly stable. in spite of this genetic stability, homologous dna recombination has been hypothesized to lie at the basis of antigenic variation of the major surface protein, p1, of m. pneumoniae. in order to identify the proteins that may be involved in homologous dna recombination in m. pneumoniae, we set out to characterize the mpn229 open reading frame (orf), which bears sequence similarity to the ...200818831760
the crystal structure of desulfovibrio vulgaris dissimilatory sulfite reductase bound to dsrc provides novel insights into the mechanism of sulfate respiration.sulfate reduction is one of the earliest types of energy metabolism used by ancestral organisms to sustain life. despite extensive studies, many questions remain about the way respiratory sulfate reduction is associated with energy conservation. a crucial enzyme in this process is the dissimilatory sulfite reductase (dsir), which contains a unique siroheme-[4fe4s] coupled cofactor. here, we report the structure of desulfoviridin from desulfovibrio vulgaris, in which the dsir dsrab (sulfite reduc ...200818829451
identification and characterization of domains responsible for self-assembly and cell wall binding of the surface layer protein of lactobacillus brevis atcc 8287.lactobacillus brevis atcc 8287 is covered by a regular surface (s-) layer consisting of a 435 amino acid protein slpa. this protein is completely unrelated in sequence to the previously characterized s-layer proteins of lactobacillus acidophilus group.200818828902
kinetic and thermodynamic studies of peptidyltransferase in ribosomes from the extreme thermophile thermus thermophilus.throughout evolution, emerging organisms survived by adapting existing biochemical processes to new reaction conditions. simple protein enzymes balanced changes in structural stability with changes that permitted optimal catalysis by adjustments in both entropic and enthalpic contributions to the free energy of activation for the reaction. study of adaptive mechanisms by large multicomponent enzymes such as the ribosome has been largely unexplored. here we have determined the kinetic and thermod ...200818824514
yeast ribosomal protein l10 helps coordinate trna movement through the large subunit.yeast ribosomal protein l10 (e. coli l16) is located at the center of a topological nexus that connects many functional regions of the large subunit. this essential protein has previously been implicated in processes as diverse as ribosome biogenesis, translational fidelity and mrna stability. here, the inability to maintain the yeast killer virus was used as a proxy for large subunit defects to identify a series of l10 mutants. these mapped to roughly four discrete regions of the protein. a det ...200818824477
protein co-evolution, co-adaptation and interactions.co-evolution has an important function in the evolution of species and it is clearly manifested in certain scenarios such as host-parasite and predator-prey interactions, symbiosis and mutualism. the extrapolation of the concepts and methodologies developed for the study of species co-evolution at the molecular level has prompted the development of a variety of computational methods able to predict protein interactions through the characteristics of co-evolution. particularly successful have bee ...200818818697
molecular characterization of organelle-type nudix hydrolases in arabidopsis.nudix (for nucleoside diphosphates linked to some moiety x) hydrolases act to hydrolyze ribonucleoside and deoxyribonucleoside triphosphates, nucleotide sugars, coenzymes, or dinucleoside polyphosphates. arabidopsis (arabidopsis thaliana) contains 27 genes encoding nudix hydrolase homologues (atnudx1 to -27) with a predicted distribution in the cytosol, mitochondria, and chloroplasts. previously, cytosolic nudix hydrolases (atnudx1 to -11 and -25) were characterized. here, we conducted a charact ...200818815383
endosymbiont gene functions impaired and rescued by polymerase infidelity at poly(a) tracts.among host-dependent bacteria that have evolved by extreme reductive genome evolution, long-term bacterial endosymbionts of insects have the smallest (160-790 kb) and most a + t-rich (>70%) bacterial genomes known to date. these genomes are riddled with poly(a) tracts, and 5-50% of genes contain tracts of 10 as or more. here, we demonstrate transcriptional slippage at poly(a) tracts within genes of buchnera aphidicola associated with aphids and blochmannia pennsylvanicus associated with ants. se ...200818815381
structural analysis of fad synthetase from corynebacterium ammoniagenes.the prokaryotic fad synthetase family - a group of bifunctional enzymes that catalyse riboflavin phosphorylation and fmn adenylylation within a single polypeptide chain- was analysed in terms of sequence and structure.200818811972
the metabolism of proline as microenvironmental stress substrate.proline, a unique proteogenic secondary amino acid, has its own metabolic system with special features. recent findings defining the regulation of this system led us to propose that proline is a stress substrate in the microenvironment of inflammation and tumorigenesis. the criteria for proline as a stress substrate are: 1) the enzymes utilizing proline respond to stress signaling; 2) there is a large, mobilizable pool of proline; and 3) the metabolism of proline serves special stress functions. ...200818806116
mechanism of 4-nitrophenol oxidation in rhodococcus sp. strain pn1: characterization of the two-component 4-nitrophenol hydroxylase and regulation of its expression.4-nitrophenol (4-np) is a toxic product of the hydrolysis of organophosphorus pesticides such as parathion in soil. rhodococcus sp. strain pn1 degrades 4-np via 4-nitrocatechol (4-nc) for use as the sole carbon, nitrogen, and energy source. a 5-kb ecori dna fragment previously cloned from pn1 contained a gene cluster (nphra1a2) involved in 4-np oxidation. from sequence analysis, this gene cluster is expected to encode an arac/xyls family regulatory protein (nphr) and a two-component 4-np hydroxy ...200818805976
mutations in conserved helix 69 of 23s rrna of thermus thermophilus that affect capreomycin resistance but not posttranscriptional modifications.translocation during the elongation phase of protein synthesis involves the relative movement of the 30s and 50s ribosomal subunits. this movement is the target of tuberactinomycin antibiotics. here, we describe the isolation and characterization of mutants of thermus thermophilus selected for resistance to the tuberactinomycin antibiotic capreomycin. two base substitutions, a1913u and mu1915g, and a single base deletion, deltamu1915, were identified in helix 69 of 23s rrna, a structural element ...200818805973
genome signature analysis of thermal virus metagenomes reveals archaea and thermophilic signatures.metagenomic analysis provides a rich source of biological information for otherwise intractable viral communities. however, study of viral metagenomes has been hampered by its nearly complete reliance on blast algorithms for identification of dna sequences. we sought to develop algorithms for examination of viral metagenomes to identify the origin of sequences independent of blast algorithms. we chose viral metagenomes obtained from two hot springs, bear paw and octopus, in yellowstone national ...200818798991
the mycobacterium tuberculosis mep (2c-methyl-d-erythritol 4-phosphate) pathway as a new drug target.tuberculosis (tb) is still a major public health problem, compounded by the human immunodeficiency virus (hiv)-tb co-infection and recent emergence of multidrug-resistant (mdr) and extensively drug resistant (xdr)-tb. novel anti-tb drugs are urgently required. in this context, the 2c-methyl-d-erythritol 4-phosphate (mep) pathway of mycobacterium tuberculosis has drawn attention; it is one of several pathways vital for m. tuberculosis viability and the human host lacks homologous enzymes. thus, t ...200918793870
the mycobacterium tuberculosis mep (2c-methyl-d-erythritol 4-phosphate) pathway as a new drug target.tuberculosis (tb) is still a major public health problem, compounded by the human immunodeficiency virus (hiv)-tb co-infection and recent emergence of multidrug-resistant (mdr) and extensively drug resistant (xdr)-tb. novel anti-tb drugs are urgently required. in this context, the 2c-methyl-d-erythritol 4-phosphate (mep) pathway of mycobacterium tuberculosis has drawn attention; it is one of several pathways vital for m. tuberculosis viability and the human host lacks homologous enzymes. thus, t ...200918793870
mass spectrometry profiles superoxide-induced intramolecular disulfide in the fmn-binding subunit of mitochondrial complex i.protein thiols with regulatory functions play a critical role in maintaining the homeostasis of the redox state in mitochondria. one major host of regulatory cysteines in mitochondria is complex i, with the thiols primarily located on its 51 kda fmn-binding subunit. in response to oxidative stress, these thiols are expected to form intramolecular disulfide bridges as one of their oxidative post-translational modifications. here, to test this hypothesis and gain insights into the molecular patter ...200818789718
rifamycins do not function by allosteric modulation of binding of mg2+ to the rna polymerase active center.rifamycin antibacterial agents inhibit bacterial rna polymerase (rnap) by binding to a site adjacent to the rnap active center and preventing synthesis of rna products >2-3 nt in length. recently, artsimovitch et al. [(2005) cell 122:351-363] proposed that rifamycins function by allosteric modulation of binding of mg(2+) to the rnap active center and presented three lines of biochemical evidence consistent with this proposal. here, we show that rifamycins do not affect the affinity of binding of ...200818787125
insights into the mode of action of a putative zinc transporter czrb in thermus thermophilus.the crystal structures of the cytoplasmic domain of the putative zinc transporter czrb in the apo and zinc-bound forms reported herein are consistent with the protein functioning in vivo as a homodimer. nmr, x-ray scattering, and size-exclusion chromatography provide support for dimer formation. full-length variants of czrb in the apo and zinc-loaded states were generated by homology modeling with the zn2+/h+ antiporter yiip. the model suggests a way in which zinc binding to the cytoplasmic frag ...200818786400
concurrent nucleation of 16s folding and induced fit in 30s ribosome assembly.rapidly growing cells produce thousands of new ribosomes each minute, in a tightly regulated process that is essential to cell growth. how the escherichia coli 16s ribosomal rna and the 20 proteins that make up the 30s ribosomal subunit can assemble correctly in a few minutes remains a challenging problem, partly because of the lack of real-time data on the earliest stages of assembly. by providing snapshots of individual rna and protein interactions as they emerge in real time, here we show tha ...200818784650
the human mitochondrial ribosome recycling factor is essential for cell viability.the molecular mechanism of human mitochondrial translation has yet to be fully described. we are particularly interested in understanding the process of translational termination and ribosome recycling in the mitochondrion. several candidates have been implicated, for which subcellular localization and characterization have not been reported. here, we show that the putative mitochondrial recycling factor, mtrrf, is indeed a mitochondrial protein. expression of human mtrrf in fission yeast devoid ...200818782833
the putative rnase p motif in the dead box helicase hera is dispensable for efficient interaction with rna and helicase activity.dead box helicases use the energy of atp hydrolysis to remodel rna structures or rna/protein complexes. they share a common helicase core with conserved signature motifs, and additional domains may confer substrate specificity. identification of a specific substrate is crucial towards understanding the physiological role of a helicase. rna binding and atpase stimulation are necessary, but not sufficient criteria for a bona fide helicase substrate. here, we report single molecule fret experiments ...200818782831
synthesis and characterization of new piperazine-type inhibitors for mitochondrial nadh-ubiquinone oxidoreductase (complex i).the mode of action of deltalac-acetogenins, strong inhibitors of bovine heart mitochondrial complex i, is different from that of traditional inhibitors such as rotenone and piericidin a [murai, m., et al. (2007) biochemistry 46 , 6409-6416]. as further exploration of these unique inhibitors might provide new insights into the terminal electron transfer step of complex i, we drastically modified the structure of deltalac-acetogenins and characterized their inhibitory action. in particular, on the ...200818781777
stabilization of alpha-chymotrypsin upon pegylation correlates with reduced structural dynamics.protein stability remains one of the main factors limiting the realization of the full potential of protein therapeutics. poly(ethylene glycol) (peg) conjugation to proteins has evolved into an important tool to overcome instability issues associated with proteins. the observed increase in thermodynamic stability of several proteins upon pegylation has been hypothesized to arise from reduced protein structural dynamics, although experimental evidence for this hypothesis is currently missing. to ...200818781698
characterization of a unique clpb protein of mycoplasma pneumoniae and its impact on growth.mycoplasma pneumoniae accounts for 20 to 30% of all community-acquired pneumonia and has been associated with other airway pathologies, including asthma, and a range of extrapulmonary manifestations. although the entire genomic sequence of m. pneumoniae has been completed, the functions of many of these genes in mycoplasma physiology are unknown. in this study, we focused on clpb, a well-known heat shock gene in other bacteria, to examine its role in mycoplasma growth. transcriptional and transl ...200818779336
structural biology of riboswitch-mediated gene regulation and argonaute-mediated gene silencing. 200818776223
editing of misaligned 3'-termini by an intrinsic 3'-5' exonuclease activity residing in the php domain of a family x dna polymerase.bacillus subtilis gene yshc encodes a family x dna polymerase (polx(bs)), whose biochemical features suggest that it plays a role during dna repair processes. here, we show that, in addition to the polymerization activity, polx(bs) possesses an intrinsic 3'-5' exonuclease activity specialized in resecting unannealed 3'-termini in a gapped dna substrate. biochemical analysis of a polx(bs) deletion mutant lacking the c-terminal polymerase histidinol phosphatase (php) domain, present in most of the ...200818776221
a novel mutator of escherichia coli carrying a defect in the dgt gene, encoding a dgtp triphosphohydrolase.a novel mutator locus in escherichia coli was identified from a collection of random transposon insertion mutants. several mutators in this collection were found to have an insertion in the dgt gene, encoding a previously characterized dgtp triphosphohydrolase. the mutator activity of the dgt mutants displays an unusual specificity. among the six possible base pair substitutions in a lacz reversion system, the g.c-->c.g transversion and a.t-->g.c transition are strongly enhanced (10- to 50-fold) ...200818776019
genetic and biochemical analysis of yeast and human cap trimethylguanosine synthase: functional overlap of 2,2,7-trimethylguanosine caps, small nuclear ribonucleoprotein components, pre-mrna splicing factors, and rna decay pathways.trimethylguanosine synthase (tgs1) is the enzyme that converts standard m(7)g caps to the 2,2,7-trimethylguanosine (tmg) caps characteristic of spliceosomal small nuclear rnas. fungi and mammalian somatic cells are able to grow in the absence of tgs1 and tmg caps, suggesting that an essential function of the tmg cap might be obscured by functional redundancy. a systematic screen in budding yeast identified nonessential genes that, when deleted, caused synthetic growth defects with tgs1delta. the ...200818775984
inhibition of a transcriptional pause by rna anchoring to rna polymerase.we describe a mechanism by which nascent rna inhibits transcriptional pausing. putl rna of bacteriophage hk022 suppresses transcription termination at downstream terminators and pausing within a nearby u-rich sequence. in vitro transcription and footprinting assays reveal that this pausing results from backtracking of rna polymerase and that binding of nascent putl rna to polymerase limits backtracking by restricting re-entry of the transcript into the rna exit channel. the restriction is local ...200818775328
mechanism of the chemical step for the guanosine triphosphate (gtp) hydrolysis catalyzed by elongation factor tu.elongation factor tu (ef-tu), the protein responsible for delivering aminoacyl-trnas (aa-trnas) to ribosomal a site during translation, belongs to the group of guanosine-nucleotide (gtp/gdp) binding proteins. its active 'on'-state corresponds to the gtp-bound form, while the inactive 'off'-state corresponds to the gdp-bound form. in this work we focus on the chemical step, gtp+h(2)o-->gdp+pi, of the hydrolysis mechanism. we apply molecular modeling tools including molecular dynamics simulations ...200818773979
full-length escherichia coli seca dimerizes in a closed conformation in solution as determined by cryo-electron microscopy.seca is an obligatory component of the escherichia coli general secretion pathway. however, the oligomeric structure of seca and seca conformational changes during translocation processes are still unclear. here we obtained the three-dimensional structure of e. coli wild-type full-length seca in solution by single particle cryo-electron microscopy and determined its oligomeric organization. in this structure, seca occurs as a dimer in which the two protomers are arranged in an antiparallel mode, ...200818772144
crystal structure of a sulfur carrier protein complex found in the cysteine biosynthetic pathway of mycobacterium tuberculosis.the structure of the protein complex cysm-cyso from a new cysteine biosynthetic pathway found in the h37rv strain of mycobacterium tuberculosis has been determined at 1.53 a resolution. cysm (rv1336) is a plp-containing beta-replacement enzyme and cyso (rv1335) is a sulfur carrier protein with a ubiquitin-like fold. cysm catalyzes the replacement of the acetyl group of o-acetylserine by cyso thiocarboxylate to generate a protein-bound cysteine that is released in a subsequent proteolysis reactio ...200818771296
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