Publications

the crystal structure of the novobiocin biosynthetic enzyme novp: the first representative structure for the tylf o-methyltransferase superfamily.	novp is an s-adenosyl-l-methionine-dependent o-methyltransferase that catalyzes the penultimate step in the biosynthesis of the aminocoumarin antibiotic novobiocin. specifically, it methylates at 4-oh of the noviose moiety, and the resultant methoxy group is important for the potency of the mature antibiotic: previous crystallographic studies have shown that this group interacts directly with the target enzyme dna gyrase, which is a validated drug target. we have determined the high-resolution c ...	2010	19857499
the crystal structure of the novobiocin biosynthetic enzyme novp: the first representative structure for the tylf o-methyltransferase superfamily.	novp is an s-adenosyl-l-methionine-dependent o-methyltransferase that catalyzes the penultimate step in the biosynthesis of the aminocoumarin antibiotic novobiocin. specifically, it methylates at 4-oh of the noviose moiety, and the resultant methoxy group is important for the potency of the mature antibiotic: previous crystallographic studies have shown that this group interacts directly with the target enzyme dna gyrase, which is a validated drug target. we have determined the high-resolution c ...	2010	19857499
allosteric control of catalysis by the f loop of rna polymerase.	bacterial rna polymerases (rnaps) undergo coordinated conformational changes during catalysis. in particular, concerted folding of the trigger loop and rearrangements of the bridge helix at the rnap active center have been implicated in nucleotide addition and rnap translocation. at moderate temperatures, the rate of catalysis by rnap from thermophilic thermus aquaticus is dramatically reduced compared with its closest mesophilic relative, deinococcus radiodurans. here, we show that a part of th ...	2009	19855007
'rna walk' a novel approach to study rna-rna interactions between a small rna and its target.	in this study we describe a novel method to investigate the rna-rna interactions between a small rna and its target that we termed 'rna walk'. the method is based on uv-induced amt cross-linking in vivo followed by affinity selection of the hybrid molecules and mapping the intermolecular adducts by rt-pcr or real-time pcr. domains carrying the cross-linked adducts fail to efficiently amplify by pcr compared with non-cross-linked domains. this method was calibrated and used to study the interacti ...	2009	19854950
'rna walk' a novel approach to study rna-rna interactions between a small rna and its target.	in this study we describe a novel method to investigate the rna-rna interactions between a small rna and its target that we termed 'rna walk'. the method is based on uv-induced amt cross-linking in vivo followed by affinity selection of the hybrid molecules and mapping the intermolecular adducts by rt-pcr or real-time pcr. domains carrying the cross-linked adducts fail to efficiently amplify by pcr compared with non-cross-linked domains. this method was calibrated and used to study the interacti ...	2009	19854950
crystallization and preliminary x-ray analysis of mannosyl-3-phosphoglycerate synthase from thermus thermophilus hb27.	mannosylglycerate (mg) is a compatible solute that is widespread in marine organisms that are adapted to hot environments, with its intracellular pool generally increasing in response to osmotic stress. these observations suggest that mg plays a relevant role in osmoadaptation and thermoadaptation. the pathways for the synthesis of mg have been characterized in a number of thermophilic and hyperthermophilic organisms. mannosyl-3-phosphoglycerate synthase (mpgs) is a key enzyme in the biosynthesi ...	2009	19851010
the structure of staphylococcus aureus phosphopantetheine adenylyltransferase in complex with 3'-phosphoadenosine 5'-phosphosulfate reveals a new ligand-binding mode.	bacterial phosphopantetheine adenylyltransferase (ppat) catalyzes the penultimate step in the coenzyme a (coa) biosynthetic pathway. it catalyzes the reversible transfer of an adenylyl group from atp to 4'-phosphopantetheine (ppant) to form dephospho-coa (dpcoa) and pyrophosphate. previous structural studies have revealed how several ligands are recognized by bacterial ppats. atp, adp, ppant and dpcoa bind to the same binding site in a highly similar manner, while coa binds to a partially overla ...	2009	19851003
yeast aep3p is an accessory factor in initiation of mitochondrial translation.	initiation of protein synthesis in mitochondria and chloroplasts normally uses a formylated initiator methionyl-trna (fmet-trna(f)(met)). however, mitochondrial protein synthesis in saccharomyces cerevisiae can initiate with nonformylated met-trna(f)(met), as demonstrated in yeast mutants in which the nuclear gene encoding mitochondrial methionyl-trna formyltransferase (fmt1) has been deleted. the role of formylation of the initiator trna is not known, but in vitro formylation increases binding ...	2009	19843529
marine-derived metabolites of s-adenosylmethionine as templates for new anti-infectives.	s-adenosylmethionine (adomet) is a key biochemical co-factor whose proximate metabolites include methylated macromolecules (e.g., nucleic acids, proteins, phospholipids), methylated small molecules (e.g., sterols, biogenic amines), polyamines (e.g., spermidine, spermine), ethylene, and n-acyl-homoserine lactones. marine organisms produce numerous adomet metabolites whose novel structures can be regarded as lead compounds for anti-infective drug design.	2009	19841722
crystal structure of the atpase domain of the human aaa+ protein paraplegin/spg7.	paraplegin is an m-aaa protease of the mitochondrial inner membrane that is linked to hereditary spastic paraplegias. the gene encodes an ftsh-homology protease domain in tandem with an aaa+ homology atpase domain. the protein is believed to form a hexamer that uses atpase-driven conformational changes in its aaa-domain to deliver substrate peptides to its protease domain. we present the crystal structure of the aaa-domain of human paraplegin bound to adp at 2.2 a. this enables assignment of the ...	2009	19841671
production of cell-cell signalling molecules by bacteria isolated from human chronic wounds.	to (i) identify chronic wound bacteria and to test their ability to produce acyl-homoserine-lactones (ahls) and autoinducer-2 (ai-2) cell-cell signalling molecules and (ii) determine whether chronic wound debridement samples might contain these molecules.	2010	19840177
production of cell-cell signalling molecules by bacteria isolated from human chronic wounds.	to (i) identify chronic wound bacteria and to test their ability to produce acyl-homoserine-lactones (ahls) and autoinducer-2 (ai-2) cell-cell signalling molecules and (ii) determine whether chronic wound debridement samples might contain these molecules.	2010	19840177
v for victory--a v1-atpase structure revealed.		2009	19834508
the crystal structure of the ribosome bound to ef-tu and aminoacyl-trna.	the ribosome selects a correct transfer rna (trna) for each amino acid added to the polypeptide chain, as directed by messenger rna. aminoacyl-trna is delivered to the ribosome by elongation factor tu (ef-tu), which hydrolyzes guanosine triphosphate (gtp) and releases trna in response to codon recognition. the signaling pathway that leads to gtp hydrolysis upon codon recognition is critical to accurate decoding. here we present the crystal structure of the ribosome complexed with ef-tu and amino ...	2009	19833920
the structure of the ribosome with elongation factor g trapped in the posttranslocational state.	elongation factor g (ef-g) is a guanosine triphosphatase (gtpase) that plays a crucial role in the translocation of transfer rnas (trnas) and messenger rna (mrna) during translation by the ribosome. we report a crystal structure refined to 3.6 angstrom resolution of the ribosome trapped with ef-g in the posttranslocational state using the antibiotic fusidic acid. fusidic acid traps ef-g in a conformation intermediate between the guanosine triphosphate and guanosine diphosphate forms. the interac ...	2009	19833919
polyamines: ubiquitous polycations with unique roles in growth and stress responses.	polyamines are small polycationic molecules found ubiquitously in all organisms and function in a wide variety of biological processes. in the past decade, molecular and genetic studies using mutants and transgenic plants with an altered activity of enzymes involved in polyamine biosynthesis have contributed much to a better understanding of the biological functions of polyamines in plants.	2009	19828463
polyamines: ubiquitous polycations with unique roles in growth and stress responses.	polyamines are small polycationic molecules found ubiquitously in all organisms and function in a wide variety of biological processes. in the past decade, molecular and genetic studies using mutants and transgenic plants with an altered activity of enzymes involved in polyamine biosynthesis have contributed much to a better understanding of the biological functions of polyamines in plants.	2009	19828463
structure, expression, and function of kynurenine aminotransferases in human and rodent brains.	kynurenine aminotransferases (kats) catalyze the synthesis of kynurenic acid (kyna), an endogenous antagonist of n-methyl-d: -aspartate and alpha 7-nicotinic acetylcholine receptors. abnormal kyna levels in human brains are implicated in the pathophysiology of schizophrenia, alzheimer's disease, and other neurological disorders. four kats have been reported in mammalian brains, kat i/glutamine transaminase k/cysteine conjugate beta-lyase 1, kat ii/aminoadipate aminotransferase, kat iii/cysteine ...	2010	19826765
structure, expression, and function of kynurenine aminotransferases in human and rodent brains.	kynurenine aminotransferases (kats) catalyze the synthesis of kynurenic acid (kyna), an endogenous antagonist of n-methyl-d: -aspartate and alpha 7-nicotinic acetylcholine receptors. abnormal kyna levels in human brains are implicated in the pathophysiology of schizophrenia, alzheimer's disease, and other neurological disorders. four kats have been reported in mammalian brains, kat i/glutamine transaminase k/cysteine conjugate beta-lyase 1, kat ii/aminoadipate aminotransferase, kat iii/cysteine ...	2010	19826765
multistart simulated annealing refinement of the crystal structure of the 70s ribosome.	a macromolecular x-ray crystal structure is usually represented as a single static model with a single set of temperature factors representing a simple approximation of motion and disorder of the structure. multiconformer representations of small proteins have been shown to better describe anisotropic motion and disorder and improve the quality of their electron density maps. here, we apply multistart simulated annealing crystallographic refinement to a 70s ribosome-rf1 translation termination c ...	2009	19822758
structural insights into rna processing by the human risc-loading complex.	targeted gene silencing by rna interference (rnai) requires loading of a short guide rna (small interfering rna (sirna) or microrna (mirna)) onto an argonaute protein to form the functional center of an rna-induced silencing complex (risc). in humans, argonaute2 (ago2) assembles with the guide rna-generating enzyme dicer and the rna-binding protein trbp to form a risc-loading complex (rlc), which is necessary for efficient transfer of nascent sirnas and mirnas from dicer to ago2. here, using sin ...	2009	19820710
acyl-coa synthesis, lipid metabolism and lipotoxicity.	although the underlying causes of insulin resistance have not been completely delineated, in most analyses, a recurring theme is dysfunctional metabolism of fatty acids. because the conversion of fatty acids to activated acyl-coas is the first and essential step in the metabolism of long-chain fatty acid metabolism, interest has grown in the synthesis of acyl-coas, their contribution to the formation of signaling molecules like ceramide and diacylglycerol, and their direct effects on cell functi ...	2009	19818872
acyl-coa synthesis, lipid metabolism and lipotoxicity.	although the underlying causes of insulin resistance have not been completely delineated, in most analyses, a recurring theme is dysfunctional metabolism of fatty acids. because the conversion of fatty acids to activated acyl-coas is the first and essential step in the metabolism of long-chain fatty acid metabolism, interest has grown in the synthesis of acyl-coas, their contribution to the formation of signaling molecules like ceramide and diacylglycerol, and their direct effects on cell functi ...	2009	19818872
features of subunit nuom (nd4) in escherichia coli ndh-1: topology and implication of conserved glu144 for coupling site 1.	the bacterial h(+)-pumping nadh-quinone oxidoreductase (ndh-1) is an l-shaped membrane-bound enzymatic complex. escherichia coli ndh-1 is composed of 13 subunits (nuoa-n). nuom (nd4) subunit is one of the hydrophobic subunits that constitute the membrane arm of ndh-1 and was predicted to bear 14 helices. we attempted to clarify the membrane topology of nuom by the introduction of histidine tags into different positions by chromosomal site-directed mutagenesis. from the data, we propose a topolog ...	2009	19815558
estimating the fraction of non-coding rnas in mammalian transcriptomes.	recent studies of mammalian transcriptomes have identified numerous rna transcripts that do not code for proteins; their identity, however, is largely unknown. here we explore an approach based on sequence randomness patterns to discern different rna classes. the relative z-score we use helps identify the known ncrna class from the genome, intergene and intron classes. this leads us to a fractional ncrna measure of putative ncrna datasets which we model as a mixture of genuine ncrnas and other t ...	2008	19812767
knowledge-based instantiation of full atomic detail into coarse-grain rna 3d structural models.	the recent development of methods for modeling rna 3d structures using coarse-grain approaches creates a need to bridge low- and high-resolution modeling methods. although they contain topological information, coarse-grain models lack atomic detail, which limits their utility for some applications.	2009	19812110
structure of a trna-dependent kinase essential for selenocysteine decoding.	compared to bacteria, archaea and eukaryotes employ an additional enzyme for the biosynthesis of selenocysteine (sec), the 21(st) natural amino acid (aa). an essential rna-dependent kinase, o-phosphoseryl-trna(sec) kinase (pstk), converts seryl-trna(sec) to o-phosphoseryl-trna(sec), the immediate precursor of selenocysteinyl-trna(sec). the sequence of methanocaldococcus jannaschii pstk (mjpstk) suggests an n-terminal kinase domain (177 aa) followed by a presumed trna binding region (75 aa). the ...	2009	19805283
the cytochrome ba3 oxygen reductase from thermus thermophilus uses a single input channel for proton delivery to the active site and for proton pumping.	the heme-copper oxygen reductases are redox-driven proton pumps that generate a proton motive force in both prokaryotes and mitochondria. these enzymes have been divided into 3 evolutionarily related groups: the a-, b- and c-families. most experimental work on proton-pumping mechanisms has been performed with members of the a-family. these enzymes require 2 proton input pathways (d- and k-channels) to transfer protons used for oxygen reduction chemistry and for proton pumping, with the d-channel ...	2009	19805275
two-dimensional pulsed electron spin resonance characterization of 15n-labeled archaeal rieske-type ferredoxin.	two-dimensional electron spin-echo envelope modulation (eseem) analysis of the uniformly (15)n-labeled archaeal rieske-type [2fe-2s] ferredoxin (arf) from sulfolobus solfataricus p1 has been conducted in comparison with the previously characterized high-potential protein homologs. major differences among these proteins were found in the hyperfine sublevel correlation (hyscore) lineshapes and intensities of the signals in the (++) quadrant, which are contributed from weakly coupled (non-coordinat ...	2009	19804777
"hot standards" for the thermoacidophilic archaeon sulfolobus solfataricus.	within the archaea, the thermoacidophilic crenarchaeote sulfolobus solfataricus has become an important model organism for physiology and biochemistry, comparative and functional genomics, as well as, more recently also for systems biology approaches. within the sulfolobus systems biology ("sulfosys")-project the effect of changing growth temperatures on a metabolic network is investigated at the systems level by integrating genomic, transcriptomic, proteomic, metabolomic and enzymatic informati ...	2010	19802714
"hot standards" for the thermoacidophilic archaeon sulfolobus solfataricus.	within the archaea, the thermoacidophilic crenarchaeote sulfolobus solfataricus has become an important model organism for physiology and biochemistry, comparative and functional genomics, as well as, more recently also for systems biology approaches. within the sulfolobus systems biology ("sulfosys")-project the effect of changing growth temperatures on a metabolic network is investigated at the systems level by integrating genomic, transcriptomic, proteomic, metabolomic and enzymatic informati ...	2010	19802714
multiple biochemical and morphological factors underlie the production of methylketones in tomato trichomes.	genetic analysis of interspecific populations derived from crosses between the wild tomato species solanum habrochaites f. sp. glabratum, which synthesizes and accumulates insecticidal methylketones (mk), mostly 2-undecanone and 2-tridecanone, in glandular trichomes, and cultivated tomato (solanum lycopersicum), which does not, demonstrated that several genetic loci contribute to mk metabolism in the wild species. a strong correlation was found between the shape of the glandular trichomes and th ...	2009	19801397
crystal structure of ynje from escherichia coli, a sulfurtransferase with three rhodanese domains.	rhodaneses/sulfurtransferases are ubiquitous enzymes that catalyze the transfer of sulfane sulfur from a donor molecule to a thiophilic acceptor via an active site cysteine that is modified to a persulfide during the reaction. here, we present the first crystal structure of a triple-domain rhodanese-like protein, namely ynje from escherichia coli, in two states where its active site cysteine is either unmodified or present as a persulfide. compared to well-characterized tandem domain rhodaneses, ...	2009	19798741
mg(2+)-dependent gating of bacterial mgte channel underlies mg(2+) homeostasis.	the mgte family of mg(2+) transporters is ubiquitously distributed in all phylogenetic domains. recent crystal structures of the full-length mgte and of its cytosolic domain in the presence and absence of mg(2+) suggested a mg(2+)-homeostasis mechanism, in which the mgte cytosolic domain acts as a 'mg(2+) sensor' to regulate the gating of the ion-conducting pore in response to the intracellular mg(2+) concentration. however, complementary functional analyses to confirm the proposed model have be ...	2009	19798051
redox characterization of the fes protein mitoneet and impact of thiazolidinedione drug binding.	mitoneet is a small mitochondrial protein that has been identified recently as a target for the thiazolidinedione (tzd) class of diabetes drugs. mitoneet also binds a unique three-cys- and one-his-ligated [corrected] [2fe-2s] cluster. here we use protein film voltammetry (pfv) as a means to probe the redox properties of mitoneet and demonstrate the direct impact of tzd drug binding upon the redox chemistry of the fes cluster. when tzds bind, the midpoint potential at ph 7 is lowered by more than ...	2009	19791753
structural studies on cytosolic domain of magnesium transporter mgte from enterococcus faecalis.		2010	19787770
tuning the properties of the bacterial membrane with aminoacylated phosphatidylglycerol.	the bacterial envelope is a semi-permeable barrier that protects the cell from the hostilities of the environment. to survive the ever-changing conditions of their surroundings, bacteria need to rapidly adjust the biochemical properties of their cellular envelope. amino acid (aa) addition to phosphatidylglycerol (pg) of the membrane is one of the mechanisms used by bacteria to lower the net negative charge of their cellular envelope, thereby decreasing its affinity for several antibacterial agen ...	2009	19787708
recode-2: new design, new search tools, and many more genes.	'recoding' is a term used to describe non-standard read-out of the genetic code, and encompasses such phenomena as programmed ribosomal frameshifting, stop codon readthrough, selenocysteine insertion and translational bypassing. although only a small proportion of genes utilize recoding in protein synthesis, accurate annotation of 'recoded' genes lags far behind annotation of 'standard' genes. in order to address this issue, provide a service to researchers in the field, and offer training data ...	2009	19783826
recode-2: new design, new search tools, and many more genes.	'recoding' is a term used to describe non-standard read-out of the genetic code, and encompasses such phenomena as programmed ribosomal frameshifting, stop codon readthrough, selenocysteine insertion and translational bypassing. although only a small proportion of genes utilize recoding in protein synthesis, accurate annotation of 'recoded' genes lags far behind annotation of 'standard' genes. in order to address this issue, provide a service to researchers in the field, and offer training data ...	2009	19783826
ion-induced folding of a kink turn that departs from the conventional sequence.	kink turns (k-turns) are important structural motifs that create a sharp axial bend in rna. most conform to a consensus in which a three-nucleotide bulge is followed by consecutive ga and ag base pairs, and when these ga pairs are modified in vitro this generally leads to a failure to adopt the k-turn conformation. kt-23 in the 30s ribosomal subunit of thermus thermophilus is a rare exception in which the bulge-distal ag pair is replaced by a non-watson-crick a*u pair. in the context of the ...	2009	19783814
inter-subunit interaction and quaternary rearrangement defined by the central stalk of prokaryotic v1-atpase.	v-type atpases (v-atpases) are categorized as rotary atp synthase/atpase complexes. the v-atpases are distinct from f-atpases in terms of their rotation scheme, architecture and subunit composition. however, there is no detailed structural information on v-atpases despite the abundant biochemical and biophysical research. here, we report a crystallographic study of v1-atpase, from thermus thermophilus, which is a soluble component consisting of a, b, d and f subunits. the structure at 4.5 a reso ...	2009	19779483
increased expression of the oxidative pentose phosphate pathway and gluconeogenesis in anaerobically growing xylose-utilizing saccharomyces cerevisiae.	fermentation of xylose to ethanol has been achieved in s. cerevisiae by genetic engineering. xylose utilization is however slow compared to glucose, and during anaerobic conditions addition of glucose has been necessary for cellular growth. in the current study, the xylose-utilizing strain tmb 3415 was employed to investigate differences between anaerobic utilization of glucose and xylose. this strain carried a xylose reductase (xyl1 k270r) engineered for increased nadh utilization and was capab ...	2009	19778438
adenosine triphosphate stimulates aquifex aeolicus mutl endonuclease activity.	background: human pms2 (hpms2) homologues act to nick 5' and 3' to misincorporated nucleotides during mismatch repair in organisms that lack muth. mn(++) was previously found to stimulate the endonuclease activity of these homologues. atp was required for the nicking activity of hpms2 and ypms1, but was reported to inhibit bacterial mutl proteins from thermus thermophilus and aquifex aeolicus that displayed homology to hpms2. mutational analysis has identified the dqha(x)(2)e(x)(4)e motif presen ...	2009	19777055
crystal structure and functional analysis of homocitrate synthase, an essential enzyme in lysine biosynthesis.	homocitrate synthase (hcs) catalyzes the first and committed step in lysine biosynthesis in many fungi and certain archaea and is a potential target for antifungal drugs. here we report the crystal structure of the hcs apoenzyme from schizosaccharomyces pombe and two distinct structures of the enzyme in complex with the substrate 2-oxoglutarate (2-og). the structures reveal that hcs forms an intertwined homodimer stabilized by domain-swapping between the n- and c-terminal domains of each monomer ...	2009	19776021
effects of protein subunits removal on the computed motions of partial 30s structures of the ribosome.	the anisotropic network model (anm) is used to study motions of the 30s small ribosomal subunit. the effect of the absence of certain subunits on the motions of the remaining partial structures was investigated by removing one protein, pairs of proteins and selected sets of proteins at a time. our results show that the removal of some proteins doesn't change the large-scale dynamics of the partial structures, but the removal of certain subunits does cause significant changes in motion of the rem ...	2008	19771145
structure of d-alanine-d-alanine ligase from thermus thermophilus hb8: cumulative conformational change and enzyme-ligand interactions.	d-alanine-d-alanine ligase (ddl) is one of the key enzymes in peptidoglycan biosynthesis and is an important target for drug discovery. the enzyme catalyzes the condensation of two d-ala molecules using atp to produce d-ala-d-ala, which is the terminal peptide of a peptidoglycan monomer. the structures of five forms of the enzyme from thermus thermophilus hb8 (ttddl) were determined: unliganded ttddl (2.3 a resolution), ttddl-adenylyl imidodiphosphate (2.6 a), ttddl-adp (2.2 a), ttddl-adp-d-ala ...	2009	19770507
zinc-independent folate biosynthesis: genetic, biochemical, and structural investigations reveal new metal dependence for gtp cyclohydrolase ib.	gtp cyclohydrolase i (gcyh-i) is an essential zn(2+)-dependent enzyme that catalyzes the first step of the de novo folate biosynthetic pathway in bacteria and plants, the 7-deazapurine biosynthetic pathway in bacteria and archaea, and the biopterin pathway in mammals. we recently reported the discovery of a new prokaryotic-specific gcyh-i (gcyh-ib) that displays no sequence identity to the canonical enzyme and is present in approximately 25% of bacteria, the majority of which lack the canonical ...	2009	19767425
exploring conformational modes of macromolecular assemblies by multiparticle cryo-em.	single particle cryo-electron microscopy (cryo-em) is a technique aimed at structure determination of large macromolecular complexes in their unconstrained, physiological conditions. the power of the method has been demonstrated in selected studies where for highly symmetric molecules the resolution attained permitted backbone tracing. however, most molecular complexes appear to exhibit intrinsic conformational variability necessary to perform their functions. therefore, it is now increasingly r ...	2009	19767196
the schizosaccharomyces pombe hsp104 disaggregase is unable to propagate the [psi] prion.	the molecular chaperone hsp104 is a crucial factor in the acquisition of thermotolerance in yeast. under stress conditions, the disaggregase activity of hsp104 facilitates the reactivation of misfolded proteins. hsp104 is also involved in the propagation of fungal prions. for instance, the well-characterized [psi(+)] prion of saccharomyces cerevisiae does not propagate in deltahsp104 cells or in cells overexpressing hsp104. in this study, we characterized the functional homolog of hsp104 from sc ...	2009	19759825
demonstration and characterization of the heterodimerization of znt5 and znt6 in the early secretory pathway.	the majority of cdf/znt zinc transporters form homo-oligomers. however, znt5, znt6, and their orthologues form hetero-oligomers in the early secretory pathway where they load zinc onto zinc-requiring enzymes and maintain secretory pathway functions. the details of this hetero-oligomerization remain to be elucidated, and much more is known about homo-oligomerization that occurs in other cdf/znt family proteins. here, we addressed this issue using co-immunoprecipitation experiments, mutagenesis, a ...	2009	19759014
recognition of trnagln by helicobacter pylori glurs2--a trnagln-specific glutamyl-trna synthetase.	accurate aminoacylation of trnas by the aminoacyl-trna synthetases (aarss) plays a critical role in protein translation. however, some of the aarss are missing in many microorganisms. helicobacter pylori does not have a glutaminyl-trna synthetase (glnrs) but has two divergent glutamyl-trna synthetases: glurs1 and glurs2. like a canonical glurs, glurs1 aminoacylates trna(glu1) and trna(glu2). in contrast, glurs2 only misacylates trna(gln) to form glu-trna(gln). it is not clear how glurs2 achieves ...	2009	19755501
in vitro metal uptake by recombinant human manganese superoxide dismutase.	metal uptake by the antioxidant defense metalloenzyme manganese superoxide dismutase (mnsod) is an essential step in the functional maturation of the protein that is just beginning to be investigated in detail. we have extended earlier in vitro studies on metal binding by the dimeric escherichia coli apo-mnsod to investigate the mechanism of metal uptake by tetrameric human and thermus thermophilus apo-mnsods. like the e. coli apo-mnsod, these proteins also bind metal ions in vitro in a thermall ...	2009	19755112
the dimeric proto-ribosome: structural details and possible implications on the origin of life.	a symmetric pocket-like entity, composed of two l-shaped rna units, encircles the peptide synthesis site within the contemporary ribosome. this entity was suggested to be the vestige of a dimeric proto-ribosome, which could have formed spontaneously in the prebiotic world, catalyzing non-coded peptide bond formation and elongation. this structural element, beyond offering the initial step in the evolution of translation, is hypothesized here to be linked to the origin of life. by catalyzing the ...	2009	19742176
dual role of dna in regulating atp hydrolysis by the sopa partition protein.	in bacteria, mitotic stability of plasmids and many chromosomes depends on replicon-specific systems, which comprise a centromere, a centromere-binding protein and an atpase. dynamic self-assembly of the atpase appears to enable active partition of replicon copies into cell-halves, but for walker-box partition atpases the molecular mechanism is unknown. atpase activity appears to be essential for this process. dna and centromere-binding proteins are known to stimulate the atpase activity but mol ...	2009	19740757
structural insights into the mechanism of the allosteric transitions of mycobacterium tuberculosis camp receptor protein.	the camp receptor protein (crp) from mycobacterium tuberculosis is a camp-responsive global transcriptional regulator, responsible for the regulation of a multitude of diverse proteins. we have determined the crystal structures of the crp.camp and crp.n(6)-camp derivative-bound forms of the enzyme to 2.2- and 2.3 a-resolution, respectively, to investigate camp-mediated conformational and structural changes. the allosteric switch from the open, inactive conformation to the closed, active conforma ...	2009	19740754
p38sj, a novel dingg protein protects neuronal cells from alcohol induced injury and death.	ethanol induces neuronal cell injury and death by dysregulating several signaling events that are controlled, in part, by activation of mapk/erk1/2 and/or inactivation of its corresponding phosphatase, pp1. recently, we have purified a novel protein of 38 kda in size, p38sj, from a callus culture of hypericum perforatum, which belongs to an emerging dingg family of proteins with phosphate binding activity. here, we show that treatment of neuronal cells with p38sj protects cells against injury in ...	2009	19739100
promiscuous substrate recognition in folding and assembly activities of the trigger factor chaperone.	trigger factor (tf) is a molecular chaperone that binds to bacterial ribosomes where it contacts emerging nascent chains, but tf is also abundant free in the cytosol where its activity is less well characterized. in vitro studies show that tf promotes protein refolding. we find here that ribosome-free tf stably associates with and rescues from misfolding a large repertoire of full-length proteins. we identify over 170 members of this cytosolic escherichia coli tf substrate proteome, including ri ...	2009	19737520
characterization of rimo, a new member of the methylthiotransferase subclass of the radical sam superfamily.	rimo, encoded by the ylig gene in escherichia coli, has been recently identified in vivo as the enzyme responsible for the attachment of a methylthio group on the beta-carbon of asp88 of the small ribosomal protein s12 [anton, b. p., saleh, l., benner, j. s., raleigh, e. a., kasif, s., and roberts, r. j. (2008) proc. natl. acad. sci. u.s.a. 105, 1826-1831]. to date, it is the only enzyme known to catalyze methylthiolation of a protein substrate; the four other naturally occurring methylthio modi ...	2009	19736993
continuous-wave and pulsed epr characterization of the [2fe-2s](cys)3(his)1 cluster in rat mitoneet.	cw epr spectra of reduced [2fe-2s](cys)(3)(his)(1) clusters of mammalian mitoneet soluble domain appear to produce features resulting from the interaction of the electron spins of the two adjacent clusters, which can be explained by employing the local spin model. this model favors the reduction of the outermost iron with his87 and cys83 ligands, which is supported by orientation-selected hyperfine sublevel correlation (hyscore) characterization of the uniformly (15)n-labeled mitoneet showing on ...	2009	19736979
the interaction of bacillus subtilis sigmaa with rna polymerase.	rna polymerase (rnap) is an essential and highly conserved enzyme in all organisms. the process of transcription initiation is fundamentally different between prokaryotes and eukaryotes. in prokaryotes, initiation is regulated by sigma factors, making the essential interaction between sigma factors and rnap an attractive target for antimicrobial agents. our objective was to achieve the first step in the process of developing novel antimicrobial agents, namely to prove experimentally that the int ...	2009	19735077
srmb, a dead-box helicase involved in escherichia coli ribosome assembly, is specifically targeted to 23s rrna in vivo.	dead-box proteins play specific roles in remodeling rna or ribonucleoprotein complexes. yet, in vitro, they generally behave as nonspecific rna-dependent atpases, raising the question of what determines their specificity in vivo. srmb, one of the five escherichia coli dead-box proteins, participates in the assembly of the large ribosomal subunit. moreover, when overexpressed, it compensates for a mutation in l24, the ribosomal protein (r-protein) thought to initiate assembly. here, using the tan ...	2009	19734346
biochemical properties and base excision repair complex formation of apurinic/apyrimidinic endonuclease from pyrococcus furiosus.	apurinic/apyrimidinic (ap) sites are the most frequently found mutagenic lesions in dna, and they arise mainly from spontaneous base loss or modified base removal by damage-specific dna glycosylases. ap sites are cleaved by ap endonucleases, and the resultant gaps in the dna are repaired by dna polymerase/dna ligase reactions. we identified the gene product that is responsible for the ap endonuclease activity in the hyperthermophilic euryarchaeon, pyrococcus furiosus. furthermore, we detected th ...	2009	19734344
identification of amino acids in the n-terminal domain of atypical methanogenic-type seryl-trna synthetase critical for trna recognition.	seryl-trna synthetase (serrs) from methanogenic archaeon methanosarcina barkeri, contains an idiosyncratic n-terminal domain, composed of an antiparallel beta-sheet capped by a helical bundle, connected to the catalytic core by a short linker peptide. it is very different from the coiled-coil trna binding domain in bacterial-type serrs. because the crystal structure of the methanogenic-type serrsxtrna complex has not been obtained, a docking model was produced, which indicated that highly conser ...	2009	19734148
the structure of eukaryotic and prokaryotic complex i.	the structures of the nadh dehydrogenases from bos taurus and aquifex aeolicus have been determined by 3d electron microscopy, and have been analyzed in comparison with the previously determined structure of complex i from yarrowia lipolytica. the results show a clearly preserved domain structure in the peripheral arm of complex i, which is similar in the bacterial and eukaryotic complex. the membrane arms of both eukaryotic complexes show a similar shape but also significant differences in dist ...	2010	19732833
the structure of eukaryotic and prokaryotic complex i.	the structures of the nadh dehydrogenases from bos taurus and aquifex aeolicus have been determined by 3d electron microscopy, and have been analyzed in comparison with the previously determined structure of complex i from yarrowia lipolytica. the results show a clearly preserved domain structure in the peripheral arm of complex i, which is similar in the bacterial and eukaryotic complex. the membrane arms of both eukaryotic complexes show a similar shape but also significant differences in dist ...	2010	19732833
a non-canonical dna structure enables homologous recombination in various genetic systems.	homologous recombination, which is critical to genetic diversity, depends on homologous pairing (hp). hp is the switch from parental to recombinant base pairs, which requires expansion of inter-base pair spaces. this expansion unavoidably causes untwisting of the parental double-stranded dna. reca/rad51-catalyzed atp-dependent hp is extensively stimulated in vitro by negative supercoils, which compensates for untwisting. however, in vivo, double-stranded dna is relaxed by bound proteins and thus ...	2009	19729448
characterization of two seryl-trna synthetases in albomycin-producing streptomyces sp. strain atcc 700974.	the trojan horse antibiotic albomycin, produced by streptomyces sp. strain atcc 700974, contains a thioribosyl nucleoside moiety linked to a hydroxamate siderophore through a serine residue. the seryl nucleoside structure (sb-217452) is a potent inhibitor of seryl-trna synthetase (serrs) in the pathogenic bacterium staphylococcus aureus, with a 50% inhibitory concentration (ic(50)) of approximately 8 nm. in the albomycin-producing streptomyces sp., a bacterial serrs homolog (alb10) was found to ...	2009	19721072
interaction of the thermoplasma acidophilum a1a0-atp synthase peripheral stalk with the catalytic domain.	the peripheral stalk of the archaeal atp synthase (a1a0)-atp synthase is formed by the heterodimeric eh complex and is part of the stator domain, which counteracts the torque of rotational catalysis. here we used nuclear magnetic resonance spectroscopy to probe the interaction of the c-terminal domain of the eh heterodimer (e(ct1)h(ct)) with the n-terminal 23 residues of the b subunit (b(nt)). the data show a specific interaction of b(nt) peptide with 26 residues of the e(ct1)h(ct) domain, there ...	2009	19720061
identification of x-ding-cd4, a new member of human ding protein family that is secreted by hiv-1 resistant cd4(+) t cells and has anti-viral activity.	we reported previously the anti-viral activity named hrf (hiv-1 resistance factor) secreted by hiv-1 resistant cells. this work describes the identification of hrf from cell culture supernatant of hrf-producing cells (hrf(+) cells). employing the proteomics and cell based activity assay we recovered ten peptides sharing 80-93% sequence homology with other eukaryotic ding proteins; discrete amino acid characteristics found in our material suggested that hrf is a new member of ding proteins family ...	2009	19720052
the yeast iron regulatory proteins grx3/4 and fra2 form heterodimeric complexes containing a [2fe-2s] cluster with cysteinyl and histidyl ligation.	the transcription of iron uptake and storage genes in saccharomyces cerevisiae is primarily regulated by the transcription factor aft1. nucleocytoplasmic shuttling of aft1 is dependent upon mitochondrial fe-s cluster biosynthesis via a signaling pathway that includes the cytosolic monothiol glutaredoxins (grx3 and grx4) and the bola homologue fra2. however, the interactions between these proteins and the iron-dependent mechanism by which they control aft1 localization are unclear. to reconstitut ...	2009	19715344
the thermus thermophilus dead box helicase hera contains a modified rna recognition motif domain loosely connected to the helicase core.	dead box family helicases consist of a helicase core that is formed by two flexibly linked reca-like domains. the helicase activity can be regulated by n- or c-terminal extensions flanking the core. thermus thermophilus heat resistant rna-dependent atpase (hera) is the first dead box helicase that forms a dimer using a unique dimerization domain. in addition to the dimerization domain, hera contains a c-terminal rna binding domain (rbd) that shares sequence homology only to uncharacterized prote ...	2009	19710183
structure of escherichia coli succinate:quinone oxidoreductase with an occupied and empty quinone-binding site.	three new structures of escherichia coli succinate-quinone oxidoreductase (sqr) have been solved. one with the specific quinone-binding site (q-site) inhibitor carboxin present has been solved at 2.4 a resolution and reveals how carboxin inhibits the q-site. the other new structures are with the q-site inhibitor pentachlorophenol and with an empty q-site. these structures reveal important details unresolved in earlier structures. comparison of the new sqr structures shows how subtle rearrangemen ...	2009	19710024
crystal structures and biochemical analyses suggest a unique mechanism and role for human glycyl-trna synthetase in ap4a homeostasis.	aminoacyl-trna synthetases catalyze the attachment of amino acids to their cognate trnas for protein synthesis. however, the aminoacylation reaction can be diverted to produce diadenosine tetraphosphate (ap4a), a universal pleiotropic signaling molecule needed for cell regulation pathways. the only known mechanism for ap4a production by a trna synthetase is through the aminoacylation reaction intermediate aminoacyl-amp, thus making ap4a synthesis amino acid-dependent. here, we demonstrate a new ...	2009	19710017
nob1 binds the single-stranded cleavage site d at the 3'-end of 18s rrna with its pin domain.	ribosome assembly is a hierarchical process that involves pre-rrna folding, modification, and cleavage and assembly of ribosomal proteins. in eukaryotes, this process requires a macromolecular complex comprising over 200 proteins and rnas. whereas the rrna modification machinery is well-characterized, rrna cleavage to release mature rrnas is poorly understood, and in yeast, only 2 of 8 endonucleases have been identified. the essential and conserved ribosome assembly factor nob1 has been suggeste ...	2009	19706509
mechanism of adp-ribosylation removal revealed by the structure and ligand complexes of the dimanganese mono-adp-ribosylhydrolase drag.	adp-ribosylation is a ubiquitous regulatory posttranslational modification involved in numerous key processes such as dna repair, transcription, cell differentiation, apoptosis, and the pathogenic mechanism of certain bacterial toxins. despite the importance of this reversible process, very little is known about the structure and mechanism of the hydrolases that catalyze removal of the adp-ribose moiety. in the phototrophic bacterium rhodospirillum rubrum, dinitrogenase reductase-activating glyc ...	2009	19706507
structure of era in complex with the 3' end of 16s rrna: implications for ribosome biogenesis.	era, composed of an n-terminal gtpase domain followed by an rna-binding kh domain, is essential for bacterial cell viability. it binds to 16s rrna and the 30s ribosomal subunit. however, its rna-binding site, the functional relationship between the two domains, and its role in ribosome biogenesis remain unclear. we have determined two crystal structures of era, a binary complex with gdp and a ternary complex with a gtp-analog and the 1531aucaccuccuua1542 sequence at the 3' end of 16s rrna. in th ...	2009	19706445
structural analysis of polarizing indels: an emerging consensus on the root of the tree of life.	the root of the tree of life has been a holy grail ever since darwin first used the tree as a metaphor for evolution. new methods seek to narrow down the location of the root by excluding it from branches of the tree of life. this is done by finding traits that must be derived, and excluding the root from the taxa those traits cover. however the two most comprehensive attempts at this strategy, performed by cavalier-smith and lake et al., have excluded each other's rootings.	2009	19706177
prokaryotic homologs of argonaute proteins are predicted to function as key components of a novel system of defense against mobile genetic elements.	in eukaryotes, rna interference (rnai) is a major mechanism of defense against viruses and transposable elements as well of regulating translation of endogenous mrnas. the rnai systems recognize the target rna molecules via small guide rnas that are completely or partially complementary to a region of the target. key components of the rnai systems are proteins of the argonaute-piwi family some of which function as slicers, the nucleases that cleave the target rna that is base-paired to a guide r ...	2009	19706170
a rubisco mutant that confers growth under a normally "inhibitory" oxygen concentration.	ribulose-1,5-bisphosphate (rubp) carboxylase/oxygenase (rubisco) is a globally significant biocatalyst that facilitates the removal and sequestration of co2 from the biosphere. rubisco-catalyzed co2 reduction thus provides virtually all of the organic carbon utilized by living organisms. despite catalyzing the rate-limiting step of photosynthetic and chemoautotrophic co2 assimilation, rubisco is markedly inefficient as the competition between o2 and co2 for the same substrate limits the ability ...	2009	19705820
phosphorylated proteins of the mammalian mitochondrial ribosome: implications in protein synthesis.	mitochondria, the powerhouse of eukaryotic cells, have their own translation machinery that is solely responsible for synthesis of 13 mitochondrially encoded protein subunits of oxidative phosphorylation complexes. phosphorylation is a well-known post-translational modification in regulation of many processes in mammalian mitochondria including oxidative phosphorylation. however, there is still very limited knowledge on phosphorylation of mitochondrial ribosomal proteins and their role(s) in rib ...	2009	19702336
a paradigm shift for the amino acid editing mechanism of human cytoplasmic leucyl-trna synthetase.	leucyl-trna synthetase (leurs) has been identified as a target for a novel class of boron-containing small molecules that bind to its editing active site. when the 3' end of trna(leu) binds to the editing active site, the boron cross-links to the cis-diols of its terminal ribose. the cross-linked rna-protein complex blocks the overall aminoacylation activity of the enzyme. similar to those of other leurss, the human cytoplasmic enzyme (hscleurs) editing active site resides in a discrete domain c ...	2009	19702327
genetic incorporation of a small, environmentally sensitive, fluorescent probe into proteins in saccharomyces cerevisiae.	here, we report that the fluorescent amino acid, 3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid (anap), can be genetically incorporated into proteins in yeast with excellent selectivity and efficiency by means of an orthogonal trna/aminoacyl-trna synthetase pair. this small, environmentally sensitive fluorophore was site-specifically incorporated into escherichia coli glutamine binding protein and used to directly probe local structural changes caused by ligand binding. the small size of ...	2009	19702307
metal uptake by manganese superoxide dismutase.	manganese superoxide dismutase is an important antioxidant defense metalloenzyme that protects cells from damage by the toxic oxygen metabolite, superoxide free radical, formed as an unavoidable by-product of aerobic metabolism. many years of research have gone into understanding how the metal cofactor interacts with small molecules in its catalytic role. in contrast, very little is presently known about how the protein acquires its metal cofactor, an important step in the maturation of the prot ...	2009	19699328
metal uptake by manganese superoxide dismutase.	manganese superoxide dismutase is an important antioxidant defense metalloenzyme that protects cells from damage by the toxic oxygen metabolite, superoxide free radical, formed as an unavoidable by-product of aerobic metabolism. many years of research have gone into understanding how the metal cofactor interacts with small molecules in its catalytic role. in contrast, very little is presently known about how the protein acquires its metal cofactor, an important step in the maturation of the prot ...	2009	19699328
formation of the first peptide bond: the structure of ef-p bound to the 70s ribosome.	elongation factor p (ef-p) is an essential protein that stimulates the formation of the first peptide bond in protein synthesis. here we report the crystal structure of ef-p bound to the thermus thermophilus 70s ribosome along with the initiator transfer rna n-formyl-methionyl-trna(i) (fmet-trna(i)(fmet)) and a short piece of messenger rna (mrna) at a resolution of 3.5 angstroms. ef-p binds to a site located between the binding site for the peptidyl trna (p site) and the exiting trna (e site). i ...	2009	19696344
immunoproteomic analysis of outer membrane proteins and extracellular proteins of actinobacillus pleuropneumoniae jl03 serotype 3.	actinobacillus pleuropneumoniae is the causative agent of porcine contagious pleuropneumonia, a highly contagious respiratory infection in pigs, and all the 15 serotypes are able to cause disease. current vaccines including subunit vaccines could not provide satisfactory protection against a. pleuropneumoniae. in this study, the immunoproteomic approach was applied to the analysis of extracellular and outer membrane proteins of a. pleuropneumoniae jl03 serotype 3 for the identification of novel ...	2009	19695095
small molecule dnak modulators targeting the beta-domain.	the molecular chaperone dnak is essential for the survival of bacterial pathogens in the hostile environment of the host. hence, it is in principle a promising target for drug design but for which no current inhibitors are available apart from certain antimicrobial peptides. to this end, we have screened libraries of small molecules for their ability to interact with the substrate-binding domain of dnak. the most promising hit from the screen was synthesized and along with its analogs subjected ...	2009	19694756
computational design of candida boidinii xylose reductase for altered cofactor specificity.	in this study we introduce a computationally-driven enzyme redesign workflow for altering cofactor specificity from nadph to nadh. by compiling and comparing data from previous studies involving cofactor switching mutations, we show that their effect cannot be explained as straightforward changes in volume, hydrophobicity, charge, or blosum62 scores of the residues populating the cofactor binding site. instead, we find that the use of a detailed cofactor binding energy approximation is needed to ...	2009	19693930
crystal structure of human selenocysteine trna.	selenocysteine (sec) is the 21st amino acid in translation. sec trna (trna(sec)) has an anticodon complementary to the uga codon. we solved the crystal structure of human trna(sec). trna(sec) has a 9-bp acceptor stem and a 4-bp t stem, in contrast with the 7-bp acceptor stem and the 5-bp t stem in the canonical trnas. the acceptor stem is kinked between the u6:u67 and g7:c66 base pairs, leading to a bent acceptor-t stem helix. trna(sec) has a 6-bp d stem and a 4-nt d loop. the long d stem includ ...	2009	19692584
the uracil dna glycosylase udgb of mycobacterium smegmatis protects the organism from the mutagenic effects of cytosine and adenine deamination.	spontaneous hydrolytic deamination of dna bases represents a considerable mutagenic threat to all organisms, particularly those living in extreme habitats. cytosine is readily deaminated to uracil, which base pairs with adenine during replication, and most organisms encode at least one uracil dna glycosylase (udg) that removes this aberrant base from dna with high efficiency. adenine deaminates to hypoxanthine approximately 10-fold less efficiently, and its removal from dna in vivo has to date b ...	2009	19684133
subcomplex ilambda specifically controls integrated mitochondrial functions in caenorhabditis elegans.	complex i dysfunction is a common, heterogeneous cause of human mitochondrial disease having poorly understood pathogenesis. the extensive conservation of complex i composition between humans and caenorhabditis elegans permits analysis of individual subunit contribution to mitochondrial functions at both the whole animal and mitochondrial levels. we provide the first experimentally-verified compilation of complex i composition in c. elegans, demonstrating 84% conservation with human complex i. i ...	2009	19672299
evolved beta-galactosidases from geobacillus stearothermophilus with improved transgalactosylation yield for galacto-oligosaccharide production.	a mutagenesis approach was applied to the beta-galactosidase bgab from geobacillus stearothermophilus kve39 in order to improve its enzymatic transglycosylation of lactose into oligosaccharides. a simple screening strategy, which was based on the reduction of the hydrolysis of a potential transglycosylation product (lactosucrose), provided mutant enzymes possessing improved synthetic properties for the autocondensation product from nitrophenyl-galactoside and galacto-oligosaccharides (gos) from ...	2009	19666723
molecular design of beta-hairpin peptides for material construction.	self-assembled materials composed of beta-sheet forming peptides hold promise as therapeutics and novel biomaterials. this article focuses on the design and engineering of amphiphilic peptide sequences, especially beta-hairpins. peptides can be designed to intramolecularly fold and then self-assemble on cue, affording hydrogels rich in beta-sheet structure. hydrogels having distinct material properties can be designed at the molecular level by modulating either the peptide's sequence or the envi ...	2008	19662109
large facilities and the evolving ribosome, the cellular machine for genetic-code translation.	well-focused x-ray beams, generated by advanced synchrotron radiation facilities, yielded high-resolution diffraction data from crystals of ribosomes, the cellular nano-machines that translate the genetic code into proteins. these structures revealed the decoding mechanism, localized the mrna path and the positions of the trna molecules in the ribosome and illuminated the interactions of the ribosome with initiation, release and recycling factors. they also showed that the ribosome is a ribozyme ...	2009	19656820
studying the salt dependence of the binding of sigma70 and sigma32 to core rna polymerase using luminescence resonance energy transfer.	the study of protein-protein interactions is becoming increasingly important for understanding the regulation of many cellular processes. the ability to quantify the strength with which two binding partners interact is desirable but the accurate determination of equilibrium binding constants is a difficult process. the use of luminescence resonance energy transfer (lret) provides a homogeneous binding assay that can be used for the detection of protein-protein interactions. previously, we develo ...	2009	19649256
selection of peptides that target the aminoacyl-trna site of bacterial 16s ribosomal rna.	for almost five decades, antibiotics have been used successfully to control infectious diseases caused by bacterial pathogens. more recently, however, two-thirds of bacterial pathogens exhibit resistance and are continually evolving new resistance mechanisms against almost every clinically used antibiotic. novel efforts are required for the development of new drugs or drug leads to combat these infectious diseases. a number of antibiotics target the bacterial aminoacyl-trna site (a site) of 16s ...	2009	19645415
hydrogen bonding and packing density are factors most strongly connected to limiting sites of high flexibility in the 16s rrna in the 30s ribosome.	conformational flexibility in structured rna frequently is critical to function. the 30s ribosomal subunit exists in different conformations in different functional states due to changes in the central part of the 16s rrna. we are interested in evaluating the factors that might be responsible for restricting flexibility to specific parts of the 16s rrna using biochemical data obtained from the 30s subunit in solution. this problem was approached taking advantage of the observation that there mus ...	2009	19643000
crystal structure of a homolog of mammalian serine racemase from schizosaccharomyces pombe.	d-serine is an endogenous coagonist for the n-methyl-d-aspartate receptor and is involved in excitatory neurotransmission in the brain. mammalian pyridoxal 5'-phosphate-dependent serine racemase, which is localized in the mammalian brain, catalyzes the racemization of l-serine to yield d-serine and vice versa. the enzyme also catalyzes the dehydration of d- and l-serine. both reactions are enhanced by mg.atp in vivo. we have determined the structures of the following three forms of the mammalian ...	2009	19640845
horizontal gene transfer of zinc and non-zinc forms of bacterial ribosomal protein s4.	the universal ribosomal protein s4 is essential for the initiation of small subunit ribosomal assembly and translational accuracy. being part of the information processing machinery of the cell, the gene for s4 is generally thought of as being inherited vertically and has been used in concatenated gene phylogenies. here we report the evolution of ribosomal protein s4 in relation to a broad sharing of zinc/non-zinc forms of the gene and study the scope of horizontal gene transfer (hgt) of s4 duri ...	2009	19640295
acyl-coa dehydrogenases: dynamic history of protein family evolution.	the acyl-coa dehydrogenases (acads) are enzymes that catalyze the alpha,beta-dehydrogenation of acyl-coa esters in fatty acid and amino acid catabolism. eleven acads are now recognized in the sequenced human genome, and several homologs have been reported from bacteria, fungi, plants, and nematodes. we performed a systematic comparative genomic study, integrating homology searches with methods of phylogenetic reconstruction, to investigate the evolutionary history of this family. sequence analys ...	2009	19639238