Publications

sesaw: balancing sequence and structural information in protein functional mapping.	motivation: functional similarity between proteins is evident at both the sequence and structure levels. sesaw is a web-based program for identifying functionally or evolutionarily conserved motifs in protein structures by locating sequence and structural similarities, and quantifying these at the level of individual residues. results can be visualized in 2d, as annotated alignments, or in 3d, as structural superpositions. an example is given for both an experimentally determined query structure ...	2010	20299324
riding in silence: a little snowboarding, a lot of small rnas.	the recent symposium, rna silencing: mechanism, biology and applications, organized by phillip d. zamore (university of massachusetts medical school) and beverly davidson (university of iowa), and held in keystone, colorado, brought together scientists working on diverse aspects of rna silencing, a field that comprises a multitude of gene regulatory pathways guided by micrornas, small interfering rnas and piwi-interacting rnas.	2010	20230614
how to slice: snapshots of argonaute in action.	abstract: argonaute is the principal protein component of the mechanisms of rna silencing, providing anchor sites for the small guide rna strand and the 'slicer' activity for cleavage of target mrnas or short passenger rna strands. argonaute is the core constituent of the silencing effector complexes risc (rna-induced silencing complex) and the rits complex (rna-induced initiation of transcriptional gene silencing complex), interacting directly or indirectly with dicer proteins, r2d2/loquacious/ ...	2010	20226069
dewetting transitions in protein cavities.	in a previous analysis of the solvation of protein active sites, a drying transition was observed in the narrow hydrophobic binding cavity of cox-2. with the use of a crude metric that often seems able to discriminate those protein cavities that dry from those that do not, we made an extensive search of the pdb, and identified five other proteins that, in molecular dynamics simulations, undergo drying transitions in their active sites. because such cavities need not desolvate before binding hydr ...	2010	20225258
potassium-activated gtpase reaction in the g protein-coupled ferrous iron transporter b.	feob is a prokaryotic membrane protein responsible for the import of ferrous iron (fe(2+)). a defining feature of feob is that it includes an n-terminal 30-kda soluble domain with gtpase activity, which is required for iron transport. however, the low intrinsic gtp hydrolysis rate of this domain appears to be too slow for feob either to function as a channel or to possess an active fe(2+) membrane transport mechanism. here, we present crystal structures of the soluble domain of feob from strepto ...	2010	20220129
dynamic effects of cofactors and dna on the oligomeric state of human mitochondrial dna helicase.	we examined the effects of cofactors and dna on the stability, oligomeric state and conformation of the human mitochondrial dna helicase. we demonstrate that low salt conditions result in protein aggregation that may cause dissociation of oligomeric structure. the low salt sensitivity of the mitochondrial dna helicase is mitigated by the presence of magnesium, nucleotide, and increased temperature. electron microscopic and glutaraldehyde cross-linking analyses provide the first evidence of a hep ...	2010	20212038
structural basis of o6-alkylguanine recognition by a bacterial alkyltransferase-like dna repair protein.	alkyltransferase-like proteins (atls) are a novel class of dna repair proteins related to o(6)-alkylguanine-dna alkyltransferases (agts) that tightly bind alkylated dna and shunt the damaged dna into the nucleotide excision repair pathway. here, we present the first structure of a bacterial atl, from vibrio parahaemolyticus (vpatl). we demonstrate that vpatl adopts an agt-like fold and that the protein is capable of tightly binding to o(6)-methylguanine-containing dna and disrupting its repair b ...	2010	20212037
isolation and purification of thermus thermophilus hpab by a crystallization approach.	the oxygenase hpab is a component of the 4-hydroxyphenylacetate 3-monooxygenase enzyme that is responsible for the hydroxylation of 4-hydroxyphenylacetate. it utilizes molecular oxygen and a reduced flavin, which is provided by hpac, the second component of the enzyme. while isolating integral membrane respiratory complexes from thermus thermophilus, microcrystals of hpab were formed. further purification of the enzyme was achieved by repetitive crystallization. subsequently, well shaped single ...	2010	20208179
crystallization and preliminary x-ray crystallographic study of phosphoglucose isomerase from plasmodium falciparum.	phosphoglucose isomerase (pgi) is a key enzyme in glycolysis and glycogenesis that catalyses the interconversion of glucose 6-phosphate (g6p) and fructose 6-phosphate (f6p). for crystallographic studies, pgi from the human malaria parasite plasmodium falciparum (pfpgi) was overproduced in escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. x-ray diffraction data to 1.5 a resolution were collected from an orthorhombic crystal form belonging to space group p ...	2010	20208175
crystallization and preliminary x-ray studies of ferredoxin-nadp+ oxidoreductase encoded by bacillus subtilis yumc.	ferredoxin-nadp(+) oxidoreductase encoded by bacillus subtilis yumc has been purified and successfully crystallized in complex with nadp(+) in two forms. diffraction data from crystals of these two forms were collected at resolutions of 1.8 and 1.9 a. the former belonged to space group p2(1)2(1)2, with unit-cell parameters a = 63.90, b = 135.72, c = 39.19 a, and the latter to space group c2, with unit-cell parameters a = 207.47, b = 64.85, c = 61.12 a, beta = 105.82 degrees. the initial structur ...	2010	20208166
the structure of dinb from geobacillus stearothermophilus: a representative of a unique four-helix-bundle superfamily.	the crystal structure of the dinb gene product from geobacillus stearothermophilus (gsdinb) is reported at 2.5 a resolution. the dinb gene is one of the dna-damage-induced genes and the corresponding protein, dinb, is the founding member of a pfam family with no known function. the protein contains a four-helix up-down-down-up bundle that has previously been described in the literature in three disparate proteins: the enzyme mdmpi (mycothiol-dependent maleylpyruvate isomerase), yfit and ttha0303 ...	2010	20208147
the crystal structure of unmodified trnaphe from escherichia coli.	post-transcriptional nucleoside modifications fine-tune the biophysical and biochemical properties of transfer rna (trna) so that it is optimized for participation in cellular processes. here we report the crystal structure of unmodified trna(phe) from escherichia coli at a resolution of 3 a. we show that in the absence of modifications the overall fold of the trna is essentially the same as that of mature trna. however, there are a number of significant structural differences, such as rearrange ...	2010	20203084
internal architecture of mitochondrial complex i from arabidopsis thaliana.	the nadh dehydrogenase complex (complex i) of the respiratory chain has unique features in plants. it is the main entrance site for electrons into the respiratory electron transfer chain, has a role in maintaining the redox balance of the entire plant cell and additionally comprises enzymatic side activities essential for other metabolic pathways. here, we present a proteomic investigation to elucidate its internal structure. arabidopsis thaliana complex i was purified by a gentle biochemical pr ...	2010	20197505
determination of ensemble-average pairwise root mean-square deviation from experimental b-factors.	root mean-square deviation (rmsd) after roto-translational least-squares fitting is a measure of global structural similarity of macromolecules used commonly. on the other hand, experimental x-ray b-factors are used frequently to study local structural heterogeneity and dynamics in macromolecules by providing direct information about root mean-square fluctuations (rmsf) that can also be calculated from molecular dynamics simulations. we provide a mathematical derivation showing that, given a set ...	2010	20197040
evolution and multifarious horizontal transfer of an alternative biosynthetic pathway for the alternative polyamine sym-homospermidine.	polyamines are small flexible organic polycations found in almost all cells. they likely existed in the last universal common ancestor of all extant life, and yet relatively little is understood about their biological function, especially in bacteria and archaea. unlike eukaryotes, where the predominant polyamine is spermidine, bacteria may contain instead an alternative polyamine, sym-homospermidine. we demonstrate that homospermidine synthase (hss) has evolved vertically, primarily in the alph ...	2010	20194510
detection of novel recombinases in bacteriophage genomes unveils rad52, rad51 and gp2.5 remote homologs.	homologous recombination is a key in contributing to bacteriophages genome repair, circularization and replication. no less than six kinds of recombinase genes have been reported so far in bacteriophage genomes, two (uvsx and gp2.5) from virulent, and four (sak, red beta, erf and sak4) from temperate phages. using profile-profile comparisons, structure-based modelling and gene-context analyses, we provide new views on the global landscape of recombinases in 465 bacteriophages. we show that sak, ...	2010	20194117
fluctuations in biological and bioinspired electron-transfer reactions.	central to theories of electron transfer (et) is the idea that nuclear motion generates a transition state that enables electron flow to proceed, but nuclear motion also induces fluctuations in the donor-acceptor (da) electronic coupling that is the rate-limiting parameter for nonadiabatic et. the interplay between the da energy gap and da coupling fluctuations is particularly noteworthy in biological et, where flexible protein and mobile water bridges take center stage. here, we discuss the cri ...	2010	20192814
partial steps of charge translocation in the nonpumping n139l mutant of rhodobacter sphaeroides cytochrome c oxidase with a blocked d-channel.	the n139l substitution in the d-channel of cytochrome oxidase from rhodobacter sphaeroides results in an approximately 15-fold decrease in the turnover number and a loss of proton pumping. time-resolved absorption and electrometric assays of the f --> o transition in the n139l mutant oxidase result in three major findings. (1) oxidation of the reduced enzyme by o(2) shows approximately 200-fold inhibition of the f --> o step (k approximately 2 s(-1) at ph 8) which is not compatible with enzyme t ...	2010	20192226
bacterial lifestyle in a deep-sea hydrothermal vent chimney revealed by the genome sequence of the thermophilic bacterium deferribacter desulfuricans ssm1.	the complete genome sequence of the thermophilic sulphur-reducing bacterium, deferribacter desulfuricans smm1, isolated from a hydrothermal vent chimney has been determined. the genome comprises a single circular chromosome of 2,234,389 bp and a megaplasmid of 308,544 bp. many genes encoded in the genome are most similar to the genes of sulphur- or sulphate-reducing bacterial species within deltaproteobacteria. the reconstructed central metabolisms showed a heterotrophic lifestyle primarily driv ...	2010	20189949
a functional peptidyl-trna hydrolase, ict1, has been recruited into the human mitochondrial ribosome.	bioinformatic analysis classifies the human protein encoded by immature colon carcinoma transcript-1 (ict1) as one of a family of four putative mitochondrial translation release factors. however, this has not been supported by any experimental evidence. as only a single member of this family, mtrf1a, is required to terminate the synthesis of all 13 mitochondrially encoded polypeptides, the true physiological function of ict1 was unclear. here, we report that ict1 is an essential mitochondrial pr ...	2010	20186120
structural and biochemical bases for the redox sensitivity of mycobacterium tuberculosis rsla.	an effective transcriptional response to redox stimuli is of particular importance for mycobacterium tuberculosis, as it adapts to the environment of host alveoli and macrophages. the m. tuberculosis sigma factor sigma(l) regulates the expression of genes involved in cell-wall and polyketide syntheses. sigma(l) interacts with the cytosolic anti-sigma domain of a membrane-associated protein, rsla. here we demonstrate that rsla binds zn(2+) and can sequester sigma(l) in a reducing environment. in ...	2010	20184899
deep phylogeny--how a tree can help characterize early life on earth.	the darwinian concept of biological evolution assumes that life on earth shares a common ancestor. the diversification of this common ancestor through speciation events and vertical transmission of genetic material implies that the classification of life can be illustrated in a tree-like manner, commonly referred to as the tree of life. this article describes features of the tree of life, such as how the tree has been both pruned and become bushier throughout the past century as our knowledge of ...	2010	20182607
para2, a vibrio cholerae chromosome partitioning protein, forms left-handed helical filaments on dna.	most bacterial chromosomes contain homologs of plasmid partitioning (par) loci. these loci encode atpases called para that are thought to contribute to the mechanical force required for chromosome and plasmid segregation. in vibrio cholerae, the chromosome ii (chrii) par locus is essential for chrii segregation. here, we found that purified para2 had atpase activities comparable to other para homologs, but, unlike many other para homologs, did not form high molecular weight complexes in the pres ...	2010	20176965
the structure of the peripheral stalk of thermus thermophilus h+-atpase/synthase.	proton-translocating atpases are ubiquitous protein complexes that couple atp catalysis with proton translocation via a rotary catalytic mechanism. the peripheral stalks are essential components that counteract torque generated from proton translocation during atp synthesis or from atp hydrolysis during proton pumping. despite their essential role, the peripheral stalks are the least conserved component of the complexes, differing substantially between subtypes in composition and stoichiometry. ...	2010	20173764
interaction of an essential escherichia coli gtpase, der, with the 50s ribosome via the kh-like domain.	der, an essential escherichia coli tandem gtpase, has been implicated in 50s subunit biogenesis. the rrmj gene encodes a methyltransferase that modifies the u2552 residue of 23s rrna, and its deletion causes a severe growth defect. peculiarly, overexpression of der suppresses growth impairment. in this study, using an rrmj-deletion strain, we demonstrated that two gtpase domains of der regulate its association with 50s subunit via the kh-like domain. we also identified a region of der that is cr ...	2010	20172997
characterization of endott, a novel single-stranded dna-specific endonuclease from thermoanaerobacter tengcongensis.	endott encoded by tte0829 of thermoanaerobacter tengcongensis binds and cleaves single-stranded (ss) and damaged double-stranded (ds) dna in vitro as well as binding dsdna. in the presence of a low concentration of nacl, endott cleaved ss regions of damaged dsdna efficiently but did not cleave dna that was entirely ss or ds. at high concentrations of nacl or mgcl(2) or atp, there was also specific cleavage of ssdna. this suggested a preference for ss/ds junctions to stimulate cleavage of the dna ...	2010	20172959
structural basis of transmembrane domain interactions in integrin signaling.	cell surface receptors of the integrin family are pivotal to cell adhesion and migration. the activation state of heterodimeric alphabeta integrins is correlated to the association state of the single-pass alpha and beta transmembrane domains. the association of integrin alphaiibbeta3 transmembrane domains, resulting in an inactive receptor, is characterized by the asymmetric arrangement of a straight (alphaiib) and tilted (beta3) helix relative to the membrane in congruence to the dissociated s ...	2010	20168080
increased incidence of rare codon clusters at 5' and 3' gene termini: implications for function.	the process of translation can be affected by the use of rare versus common codons within the mrna transcript.	2010	20167116
multiple controls affect arsenite oxidase gene expression in herminiimonas arsenicoxydans.	both the speciation and toxicity of arsenic are affected by bacterial transformations, i.e. oxidation, reduction or methylation. these transformations have a major impact on environmental contamination and more particularly on arsenic contamination of drinking water. herminiimonas arsenicoxydans has been isolated from an arsenic- contaminated environment and has developed various mechanisms for coping with arsenic, including the oxidation of as(iii) to as(v) as a detoxification mechanism.	2010	20167112
electron flow through proteins.	electron transfers in photosynthesis and respiration commonly occur between metal-containing cofactors that are separated by large molecular distances. employing laser flash-quench triggering methods, we have shown that 20-å, coupling-limited fe(ii) to ru(iii) and cu(i) to ru(iii) electron tunneling in ru-modified cytochromes and blue copper proteins can occur on the microsecond timescale both in solutions and crystals. redox equivalents can be transferred even longer distances by multistep tunn ...	2009	20161522
cell-specific differences in the requirements for translation quality control.	protein synthesis has an overall error rate of approximately 10(-4) for each mrna codon translated. the fidelity of translation is mainly determined by two events: synthesis of cognate amino acid:trna pairs by aminoacyl-trna synthetases (aarss) and accurate selection of aminoacyl-trnas (aa-trnas) by the ribosome. to ensure faithful aa-trna synthesis, many aarss employ a proofreading ("editing") activity, such as phenylalanyl-trna synthetases (phers) that hydrolyze mischarged tyr-trna(phe). eukar ...	2010	20160120
exit strategies for charged trna from glurs.	for several class i aminoacyl-trna synthetases (aarss), the rate-determining step in aminoacylation is the dissociation of charged trna from the enzyme. in this study, the following factors affecting the release of the charged trna from aarss are computationally explored: the protonation states of amino acids and substrates present in the active site, and the presence and the absence of amp and elongation factor tu. through molecular modeling, internal pk(a) calculations, and molecular dynamics ...	2010	20156451
friedreich ataxia: molecular mechanisms, redox considerations, and therapeutic opportunities.	mitochondrial dysfunction and oxidative damage are at the origin of numerous neurodegenerative diseases like friedreich ataxia and alzheimer and parkinson diseases. friedreich ataxia (frda) is the most common hereditary ataxia, with one individual affected in 50,000. this disease is characterized by progressive degeneration of the central and peripheral nervous systems, cardiomyopathy, and increased incidence of diabetes mellitus. frda is caused by a dynamic mutation, a gaa trinucleotide repeat ...	2010	20156111
the structures of the anti-tuberculosis antibiotics viomycin and capreomycin bound to the 70s ribosome.	viomycin and capreomycin belong to the tuberactinomycin family of antibiotics, which are among the most effective antibiotics against multidrug-resistant tuberculosis. here we present two crystal structures of the 70s ribosome in complex with three trnas and bound to either viomycin or capreomycin at 3.3- and 3.5-a resolution, respectively. both antibiotics bind to the same site on the ribosome, which lies at the interface between helix 44 of the small ribosomal subunit and helix 69 of the large ...	2010	20154709
aminoglycoside activity observed on single pre-translocation ribosome complexes.		2010	20154669
organization of the electron transfer chain to oxygen in the obligate human pathogen neisseria gonorrhoeae: roles for cytochromes c4 and c5, but not cytochrome c2, in oxygen reduction.	although neisseria gonorrhoeae is a prolific source of eight c-type cytochromes, little is known about how its electron transfer pathways to oxygen are organized. in this study, the roles in the respiratory chain to oxygen of cytochromes c(2), c(4), and c(5), encoded by the genes ccca, cyca, and cycb, respectively, have been investigated. single mutations in genes for either cytochrome c(4) or c(5) resulted in an increased sensitivity to growth inhibition by excess oxygen and small decreases in ...	2010	20154126
kinetic and structural characterization of human mortalin.	human mortalin is an hsp70 chaperone that has been implicated in cancer, alzheimer's and parkinson's disease, and involvement has been suggested in cellular iron-sulfur cluster biosynthesis. however, study of this important human chaperone has been hampered by a lack of active material sufficient for biochemical characterization. herein, we report the successful purification and characterization of recombinant human mortalin in escherichia coli. the recombinant protein was expressed in the form ...	2010	20152901
plasticity of the rna kink turn structural motif.	the kink turn (k-turn) is an rna structural motif found in many biologically significant rnas. while most examples of the k-turn have a similar fold, the crystal structure of the azoarcus group i intron revealed a novel rna conformation, a reverse kink turn bent in the direction opposite that of a consensus k-turn. the reverse k-turn is bent toward the major grooves rather than the minor grooves of the flanking helices, yet the sequence differs from the k-turn consensus by only a single nucleoti ...	2010	20145044
protein vivisection reveals elusive intermediates in folding.	although most folding intermediates escape detection, their characterization is crucial to the elucidation of folding mechanisms. here, we outline a powerful strategy to populate partially unfolded intermediates: a buried aliphatic residue is substituted with a charged residue (e.g., leu-->glu(-)) to destabilize and unfold a specific region of the protein. we applied this strategy to ubiquitin, reversibly trapping a folding intermediate in which the beta5-strand is unfolded. the intermediate ref ...	2010	20144618
homopolymeric tracts represent a general regulatory mechanism in prokaryotes.	while, traditionally, regulation of gene expression can be grouped into transcriptional, translational, and post-translational mechanisms, some mechanisms of rapid genetic variation can also contribute to regulation of gene expression, e.g., phase variation.	2010	20144225
muts and mutl are dispensable for maintenance of the genomic mutation rate in the halophilic archaeon halobacterium salinarum nrc-1.	the genome of the halophilic archaeon halobacterium salinarum nrc-1 encodes for homologs of muts and mutl, which are key proteins of a dna mismatch repair pathway conserved in bacteria and eukarya. mismatch repair is essential for retaining the fidelity of genetic information and defects in this pathway result in the deleterious accumulation of mutations and in hereditary diseases in humans.	2010	20140215
crystal structure of the bifunctional proline utilization a flavoenzyme from bradyrhizobium japonicum.	the bifunctional proline catabolic flavoenzyme, proline utilization a (puta), catalyzes the oxidation of proline to glutamate via the sequential activities of fad-dependent proline dehydrogenase (prodh) and nad(+)-dependent delta(1)-pyrroline-5-carboxylate dehydrogenase (p5cdh) domains. although structures for some of the domains of puta are known, a structure for the full-length protein has not previously been solved. here we report the 2.1 a resolution crystal structure of puta from bradyrhizo ...	2010	20133651
crystal structures of trypanosomal histidyl-trna synthetase illuminate differences between eukaryotic and prokaryotic homologs.	crystal structures of histidyl-trna synthetase (hisrs) from the eukaryotic parasites trypanosoma brucei and trypanosoma cruzi provide a first structural view of a eukaryotic form of this enzyme and reveal differences from bacterial homologs. hisrss in general contain an extra domain inserted between conserved motifs 2 and 3 of the class ii aminoacyl-trna synthetase catalytic core. the current structures show that the three-dimensional topology of this domain is very different in bacterial and ar ...	2010	20132829
functional regions of the n-terminal domain of the antiterminator rfah.	rfah is a bacterial elongation factor that increases expression of distal genes in several long, horizontally acquired operons. rfah is recruited to the transcription complex during rna chain elongation through specific interactions with a dna element called ops. following recruitment, rfah remains bound to rna polymerase (rnap) and acts as an antiterminator by reducing rnap pausing and termination at some factor-independent and rho-dependent signals. rfah consists of two domains connected by a ...	2010	20132437
structure of recj exonuclease defines its specificity for single-stranded dna.	recj is a single-stranded dna (ssdna)-specific 5'-3' exonuclease that plays an important role in dna repair and recombination. to elucidate how recj achieves its high specificity for ssdna, we determined the entire structures of recj both in a ligand-free form and in a complex with mn(2+) or mg(2+) by x-ray crystallography. the entire recj consists of four domains that form a molecule with an o-like structure. one of two newly identified domains had structural similarities to an oligonucleotide/ ...	2010	20129927
the crispr system: small rna-guided defense in bacteria and archaea.	all cellular systems evolve ways to combat predators and genomic parasites. in bacteria and archaea, numerous resistance mechanisms have developed against phage. our understanding of this defensive repertoire has recently been expanded to include the crispr system of clustered, regularly interspaced short palindromic repeats. in this remarkable pathway, short sequence tags from invading genetic elements are actively incorporated into the host's crispr locus to be transcribed and processed into a ...	2010	20129051
identification of the tirandamycin biosynthetic gene cluster from streptomyces sp. 307-9.	the structurally intriguing bicyclic ketal moiety of tirandamycin is common to several acyl-tetramic acid antibiotics, and is a key determinant of biological activity. we have identified the tirandamycin biosynthetic gene cluster from the environmental marine isolate streptomyces sp. 307-9, thus providing the first genetic insight into the biosynthesis of this natural product scaffold. sequence analysis revealed a hybrid polyketide synthase-nonribosomal peptide synthetase gene cluster with a col ...	2010	20127927
crispr interference: rna-directed adaptive immunity in bacteria and archaea.	sequence-directed genetic interference pathways control gene expression and preserve genome integrity in all kingdoms of life. the importance of such pathways is highlighted by the extensive study of rna interference (rnai) and related processes in eukaryotes. in many bacteria and most archaea, clustered, regularly interspaced short palindromic repeats (crisprs) are involved in a more recently discovered interference pathway that protects cells from bacteriophages and conjugative plasmids. crisp ...	2010	20125085
crystallization and preliminary x-ray diffraction analyses of the homodimeric glycine decarboxylase (p-protein) from the cyanobacterium synechocystis sp. pcc 6803.	glycine decarboxylase, or p-protein, is a major enzyme that is involved in the c(1) metabolism of all organisms and in the photorespiratory pathway of plants and cyanobacteria. the protein from synechocystis sp. pcc 6803 is a homodimer with a mass of 215 kda. recombinant glycine decarboxylase was expressed in escherichia coli and purified by metal-affinity, ion-exchange and gel-filtration chromatography. crystals of p-protein that diffracted to a resolution of 2.1 a were obtained using the hangi ...	2010	20124719
crystal structure of the first eubacterial mre11 nuclease reveals novel features that may discriminate substrates during dna repair.	mre11 nuclease plays a central role in the repair of cytotoxic and mutagenic dna double-strand breaks. as x-ray structural information has been available only for the pyrococcus furiosus enzyme (pfmre11), the conserved and variable features of this nuclease across the domains of life have not been experimentally defined. our crystal structure and biochemical studies demonstrate that tm1635 from thermotoga maritima, originally annotated as a putative nuclease, is an mre11 endo/exonuclease (tmmre1 ...	2010	20122942
improving small-angle x-ray scattering data for structural analyses of the rna world.	defining the shape, conformation, or assembly state of an rna in solution often requires multiple investigative tools ranging from nucleotide analog interference mapping to x-ray crystallography. a key addition to this toolbox is small-angle x-ray scattering (saxs). saxs provides direct structural information regarding the size, shape, and flexibility of the particle in solution and has proven powerful for analyses of rna structures with minimal requirements for sample concentration and volumes. ...	2010	20106957
the regulatory protein rraa modulates rna-binding and helicase activities of the e. coli rna degradosome.	the escherichia coli endoribonuclease rnase e is an essential enzyme having key roles in mrna turnover and the processing of several structured rna precursors, and it provides the scaffold to assemble the multienzyme rna degradosome. the activity of rnase e is inhibited by the protein rraa, which can interact with the ribonuclease's degradosome-scaffolding domain. here, we report that rraa can bind to the rna helicase component of the degradosome (rhlb) and the two rna-binding sites in the degra ...	2010	20106955
genome scale prediction of substrate specificity for acyl adenylate superfamily of enzymes based on active site residue profiles.	enzymes belonging to acyl:coa synthetase (acs) superfamily activate wide variety of substrates and play major role in increasing the structural and functional diversity of various secondary metabolites in microbes and plants. however, due to the large sequence divergence within the superfamily, it is difficult to predict their substrate preference by annotation transfer from the closest homolog. therefore, a large number of acs sequences present in public databases lack any functional annotation ...	2010	20105319
a major role of the recfor pathway in dna double-strand-break repair through esdsa in deinococcus radiodurans.	in deinococcus radiodurans, the extreme resistance to dna-shattering treatments such as ionizing radiation or desiccation is correlated with its ability to reconstruct a functional genome from hundreds of chromosomal fragments. the rapid reconstitution of an intact genome is thought to occur through an extended synthesis-dependent strand annealing process (esdsa) followed by dna recombination. here, we investigated the role of key components of the recf pathway in esdsa in this organism naturall ...	2010	20090937
structural basis for l-lysine feedback inhibition of homocitrate synthase.	the alpha-aminoadipate pathway of lysine biosynthesis is modulated at the transcriptional and biochemical levels by feedback inhibition. the first enzyme in the alpha-aminoadipate pathway, homocitrate synthase (hcs), is the target of the feedback regulation and is strongly inhibited by l-lysine. here we report the structure of schizosaccharomyces pombe hcs (sphcs) in complex with l-lysine. the structure illustrates that the amino acid directly competes with the substrate 2-oxoglutarate for bindi ...	2010	20089861
new, closely related haloarchaeal viral elements with different nucleic acid types.	during the search for haloarchaeal viruses, we isolated and characterized a new pleomorphic lipid-containing virus, haloarcula hispanica pleomorphic virus 1 (hhpv-1), that infects the halophilic archaeon haloarcula hispanica. the virus contains a circular double-stranded dna genome of 8,082 bp in size. the organization of the genome shows remarkable synteny and amino acid sequence similarity to the genome and predicted proteins of the halovirus hrpv-1, a pleomorphic single-stranded dna virus tha ...	2010	20089654
the path to next generation biofuels: successes and challenges in the era of synthetic biology.	volatility of oil prices along with major concerns about climate change, oil supply security and depleting reserves have sparked renewed interest in the production of fuels from renewable resources. recent advances in synthetic biology provide new tools for metabolic engineers to direct their strategies and construct optimal biocatalysts for the sustainable production of biofuels. metabolic engineering and synthetic biology efforts entailing the engineering of native and de novo pathways for con ...	2010	20089184
properties of escherichia coli ef-tu mutants designed for fluorescence resonance energy transfer from trna molecules.	here we describe the design, preparation and characterization of 10 ef-tu mutants of potential utility for the study of escherichia coli elongation factor tu (ef-tu) interaction with trna by a fluorescence resonance energy transfer assay. each mutant contains a single cysteine residue at positions in ef-tu that are proximal to trna sites within the aminoacyl-trna.ef-tu.gtp ternary complex that have previously been labeled with fluorophores. these positions fall in the 323-326 and 344-348 regions ...	2010	20083494
temperature dependence of the flexibility of thermophilic and mesophilic flavoenzymes of the nitroreductase fold.	a widely held hypothesis regarding the thermostability of thermophilic proteins states asserts that, at any given temperature, thermophilic proteins are more rigid than their mesophilic counterparts. many experimental and computational studies have addressed this question with conflicting results. here, we compare two homologous enzymes, one mesophilic (escherichia coli fmn-dependent nitroreductase; ntr) and one thermophilic (thermus thermophilus nadh oxidase; nox), by multiple molecular dynamic ...	2010	20083491
structure of intact thermus thermophilus v-atpase by cryo-em reveals organization of the membrane-bound v(o) motor.	the eubacterium thermus thermophilus uses a macromolecular assembly closely related to eukaryotic v-atpase to produce its supply of atp. this simplified v-atpase offers several advantages over eukaryotic v-atpases for structural analysis and investigation of the mechanism of the enzyme. here we report the structure of the complex at approximately 16 a resolution as determined by single particle electron cryomicroscopy (cryo-em). the resolution of the map and our use of cryo-em, rather than negat ...	2010	20080582
unique features of animal mitochondrial translation systems. the non-universal genetic code, unusual features of the translational apparatus and their relevance to human mitochondrial diseases.	in animal mitochondria, several codons are non-universal and their meanings differ depending on the species. in addition, the trna structures that decipher codons are sometimes unusually truncated. these features seem to be related to the shortening of mitochondrial (mt) genomes, which occurred during the evolution of mitochondria. these organelles probably originated from the endosymbiosis of an aerobic eubacterium into an ancestral eukaryote. it is plausible that these events brought about the ...	2010	20075606
the nd2 subunit is labeled by a photoaffinity analogue of asimicin, a potent complex i inhibitor.	nadh:ubiquinone oxidoreductase (complex i) is the entry enzyme of mitochondrial oxidative phosphorylation. to obtain the structural information on inhibitor/quinone binding sites, we synthesized [3h]benzophenone-asimicin ([3h]bpa), a photoaffinity analogue of asimicin, which belongs to the acetogenin family known as the most potent complex i inhibitor. we found that [3h]bpa was photo-crosslinked to nd2, nd1 and nd5 subunits, by the three dimensional separation (blue-native/doubled sds-page) of [ ...	2010	20074573
telomere-centromere-driven genomic instability contributes to karyotype evolution in a mouse model of melanoma.	aneuploidy and chromosomal instability (cin) are hallmarks of most solid tumors. these alterations may result from inaccurate chromosomal segregation during mitosis, which can occur through several mechanisms including defective telomere metabolism, centrosome amplification, dysfunctional centromeres, and/or defective spindle checkpoint control. in this work, we used an in vitro murine melanoma model that uses a cellular adhesion blockade as a transforming factor to characterize telomeric and ce ...	2010	20072649
genome comparison and context analysis reveals putative mobile forms of restriction-modification systems and related rearrangements.	the mobility of restriction-modification (rm) gene complexes and their association with genome rearrangements is a subject of active investigation. here we conducted systematic genome comparisons and genome context analysis on fully sequenced prokaryotic genomes to detect rm-linked genome rearrangements. rm genes were frequently found to be linked to mobility-related genes such as integrase and transposase homologs. they were flanked by direct and inverted repeats at a significantly high frequen ...	2010	20071371
predicting the pathway involved in post-translational modification of elongation factor p in a subset of bacterial species.	background: the bacterial elongation factor p (ef-p) is strictly conserved in bacteria and essential for protein synthesis. it is homologous to the eukaryotic translation initiation factor 5a (eif5a). a highly conserved eif5a lysine is modified into an unusual amino acid derived from spermidine, hypusine. hypusine is absolutely required for eif5a's role in translation in saccharomyces cerevisiae. the homologous lysine of ef-p is also modified to a spermidine derivative in escherichia coli. howev ...	2010	20070887
an active dimanganese(iii)-tyrosyl radical cofactor in escherichia coli class ib ribonucleotide reductase.	escherichia coli class ib ribonucleotide reductase (rnr) converts nucleoside 5'-diphosphates to deoxynucleoside 5'-diphosphates and is expressed under iron-limited and oxidative stress conditions. this rnr is composed of two homodimeric subunits: alpha2 (nrde), where nucleotide reduction occurs, and beta2 (nrdf), which contains an unidentified metallocofactor that initiates nucleotide reduction. nrde and nrdf are found in an operon with nrdi, which encodes an unusual flavodoxin proposed to be in ...	2010	20070127
role of copper ion in regulating ligand binding in a myoglobin-based cytochrome c oxidase model.	cytochrome c oxidase (cco), the terminal enzyme in the mitochondrial respiratory chain, catalyzes the four-electron reduction of dioxygen to water in a binuclear center comprised of a high-spin heme (heme a(3)) and a copper atom (cu(b)) coordinated by three histidine residues. as a minimum model for cco, a mutant of sperm whale myoglobin, named cu(b)mb, has been engineered, in which a copper atom is held in the distal heme pocket by the native e7 histidine and two nonnative histidine residues. i ...	2010	20070118
crystallization and preliminary x-ray crystallographic analysis of thermus thermophilus transcription elongation complex bound to gfh1.	rna polymerase (rnap) elongates rna by iterative nucleotide-addition cycles (nac). a specific structural state (or states) of rnap may be the target of transcription elongation factors. gfh1, a thermus thermophilus gre-family protein, inhibits nac. to elucidate which rnap structural state gfh1 associates with, the t. thermophilus rnap elongation complex (ec) was cocrystallized with gfh1. of the 70 dna/rna scaffolds tested, two (for ec1 and ec2) were successfully crystallized. in the presence of ...	2010	20057074
crystallization and preliminary x-ray crystallographic analysis of dna gyrase gyrb subunit from xanthomonas oryzae pv. oryzae.	dna gyrase is a type ii topoisomerase that is essential for chromosome segregation and cell division owing to its ability to modify the topological forms of bacterial dna. in this study, the n-terminal fragment of the gyrb subunit of dna gyrase from xanthomonas oryzae pv. oryzae was overexpressed in escherichia coli, purified and crystallized. diffraction data were collected to 2.10 a resolution using a synchrotron-radiation source. the crystal belonged to space group i4(1), with unit-cell param ...	2010	20057069
crystallization and preliminary x-ray crystallographic analysis of dna gyrase gyrb subunit from xanthomonas oryzae pv. oryzae.	dna gyrase is a type ii topoisomerase that is essential for chromosome segregation and cell division owing to its ability to modify the topological forms of bacterial dna. in this study, the n-terminal fragment of the gyrb subunit of dna gyrase from xanthomonas oryzae pv. oryzae was overexpressed in escherichia coli, purified and crystallized. diffraction data were collected to 2.10 a resolution using a synchrotron-radiation source. the crystal belonged to space group i4(1), with unit-cell param ...	2010	20057069
structure and ligand binding properties of the epoxidase component of styrene monooxygenase .	styrene monooxygenase (smo) is a two-component flavoprotein monooxygenase that transforms styrene to styrene oxide in the first step of the styrene catabolic and detoxification pathway of pseudomonas putida s12. the crystal structure of the n-terminally histidine-tagged epoxidase component of this system, nsmoa, determined to 2.3 a resolution, indicates the enzyme exists as a homodimer in which each monomer forms two distinct domains. the overall architecture is most similar to that of p-hydroxy ...	2010	20055497
multifrequency epr studies of manganese catalases provide a complete description of proteinaceous nitrogen coordination.	pulse electron paramagnetic resonance (epr) spectroscopy is employed at two very different excitation frequencies, 9.77 and 30.67 ghz, in the study of the nitrogen coordination environment of the mn(iii)mn(iv) state of the dimanganese-containing catalases from lactobacillus plantarum and thermus thermophilus. consistent with previous studies, the lower-frequency results reveal one unique histidine nitrogen-mn cluster interaction. for the first time, a second, more strongly hyperfine-coupled (14) ...	2010	20055466
structure of putative 4-amino-4-deoxychorismate lyase from thermus thermophilus hb8.	the pyridoxal 5'-phosphate-dependent enzyme 4-amino-4-deoxychorismate lyase converts 4-amino-4-deoxychorismate to p-aminobenzoate and pyruvate in one of the crucial steps in the folate-biosynthesis pathway. the primary structure of the hypothetical protein ttha0621 from thermus thermophilus hb8 suggests that ttha0621 is a putative 4-amino-4-deoxychorismate lyase. here, the crystal structure of ttha0621 is reported at 1.93 a resolution. the asymmetric unit contained four ncs molecules related by ...	2009	20054118
structure of sure protein from aquifex aeolicus vf5 at 1.5 a resolution.	sure is a stationary-phase survival protein found in bacteria, eukaryotes and archaea that exhibits a divalent-metal-ion-dependent phosphatase activity and acts as a nucleotidase and polyphosphate phosphohydrolase. the structure of the sure protein from the hyperthermophile aquifex aeolicus has been solved at 1.5 a resolution using molecular replacement with one dimer in the asymmetric unit and refined to an r factor of 15.6%. the crystal packing reveals that two dimers assemble to form a tetram ...	2009	20054112
flexible recognition of the trna g18 methylation target site by trmh methyltransferase through first binding and induced fit processes.	transfer rna (gm18) methyltransferase (trmh) catalyzes methyl transfer from s-adenosyl-l-methionine to a conserved g18 in trna. we investigated the recognition mechanism of thermus thermophilus trmh for its guanosine target. thirteen yeast trna(phe) mutant transcripts were prepared in which the modification site and/or other nucleotides in the d-loop were substituted by dg, inosine, or other nucleotides. we then conducted methyl transfer kinetic studies, gel shift assays, and inhibition experime ...	2010	20053984
structural insights into rna interference.	virtually all animals and plants utilize small rna molecules to control protein expression during different developmental stages and in response to viral infection. structural and mechanistic studies have begun to illuminate three fundamental aspects of these pathways: small rna biogenesis, formation of rna-induced silencing complexes (riscs), and targeting of complementary mrnas. here we review exciting recent progress in understanding how regulatory rnas are produced and how they trigger speci ...	2010	20053548
assessing the quality of whole genome alignments in bacteria.	comparing genomes is an essential preliminary step to solve many problems in biology. matching long similar segments between two genomes is a precondition for their evolutionary, genetic, and genome rearrangement analyses. though various comparison methods have been developed in recent years, a quantitative assessment of their performance is lacking. here, we describe two families of assessment measures whose purpose is to evaluate bacteria-oriented comparison tools. the first measure is based o ...	2009	20049164
thermodynamic characterization of naturally occurring rna tetraloops.	although tetraloops are one of the most frequently occurring secondary structure motifs in rna, less than one-third of the 30 most frequently occurring rna tetraloops have been thermodynamically characterized. therefore, 24 stem-loop sequences containing common tetraloops were optically melted, and the thermodynamic parameters deltah degrees , deltas degrees , deltag degrees (37,) and t(m) for each stem-loop were determined. these new experimental values, on average, are 0.7 kcal/mol different f ...	2010	20047989
the chlamydial functional homolog of ksga confers kasugamycin sensitivity to chlamydia trachomatis and impacts bacterial fitness.	rrna adenine dimethyltransferases, represented by the escherichia coli ksga protein, are highly conserved phylogenetically and are generally not essential for growth. they are responsible for the post-transcriptional transfer of two methyl groups to two universally conserved adenosines located near the 3'end of the small subunit rrna and participate in ribosome maturation. all sequenced genomes of chlamydia reveal a ksga homolog in each species, including c. trachomatis. yet absence of a s-adeno ...	2009	20043826
filling the gap, evolutionarily conserved omp85 in plastids of chromalveolates.	chromalveolates are a diverse group of protists that include many ecologically and medically relevant organisms such as diatoms and apicomplexan parasites. they possess plastids generally surrounded by four membranes, which evolved by engulfment of a red alga. today, most plastid proteins must be imported, but many aspects of protein import into complex plastids are still cryptic. in particular, how proteins cross the third outermost membrane has remained unexplained. we identified a protein in ...	2010	20042599
filling the gap, evolutionarily conserved omp85 in plastids of chromalveolates.	chromalveolates are a diverse group of protists that include many ecologically and medically relevant organisms such as diatoms and apicomplexan parasites. they possess plastids generally surrounded by four membranes, which evolved by engulfment of a red alga. today, most plastid proteins must be imported, but many aspects of protein import into complex plastids are still cryptic. in particular, how proteins cross the third outermost membrane has remained unexplained. we identified a protein in ...	2010	20042599
discovery of 3-formyl-tyrosine metabolites from pseudoalteromonas tunicata through heterologous expression.	genome mining and identification of natural product gene clusters typically relies on the presence of canonical nonribosomal polypeptide synthetase (nrps) or polyketide synthase (pks) domains. recently, other condensation enzymes, such as the atp-grasp ligases, have been recognized as important players in natural product biosynthesis. in this study, sequence based searching for homologues of ddaf, the atp-grasp amide ligase from dapdiamide biosynthesis, led to the identification of a previously ...	2010	20041686
discovery of 3-formyl-tyrosine metabolites from pseudoalteromonas tunicata through heterologous expression.	genome mining and identification of natural product gene clusters typically relies on the presence of canonical nonribosomal polypeptide synthetase (nrps) or polyketide synthase (pks) domains. recently, other condensation enzymes, such as the atp-grasp ligases, have been recognized as important players in natural product biosynthesis. in this study, sequence based searching for homologues of ddaf, the atp-grasp amide ligase from dapdiamide biosynthesis, led to the identification of a previously ...	2010	20041686
identification and biochemical characterization of molybdenum cofactor-binding proteins from arabidopsis thaliana.	the molybdenum cofactor (moco) forms part of the catalytic center in all eukaryotic molybdenum enzymes and is synthesized in a highly conserved pathway. among eukaryotes, very little is known about the processes taking place subsequent to moco biosynthesis, i.e. moco transfer, allocation, and insertion into molybdenum enzymes. in the model plant arabidopsis thaliana, we identified a novel protein family consisting of nine members that after recombinant expression are able to bind moco with k(d) ...	2009	20040598
identification and biochemical characterization of molybdenum cofactor-binding proteins from arabidopsis thaliana.	the molybdenum cofactor (moco) forms part of the catalytic center in all eukaryotic molybdenum enzymes and is synthesized in a highly conserved pathway. among eukaryotes, very little is known about the processes taking place subsequent to moco biosynthesis, i.e. moco transfer, allocation, and insertion into molybdenum enzymes. in the model plant arabidopsis thaliana, we identified a novel protein family consisting of nine members that after recombinant expression are able to bind moco with k(d) ...	2009	20040598
helix insertion into bilayers and the evolution of membrane proteins.	polytopic alpha-helical membrane proteins cannot spontaneously insert into lipid bilayers without assistance from polytopic alpha-helical membrane proteins that already reside in the membrane. this raises the question of how these proteins evolved. our current knowledge of the insertion of alpha-helices into natural and model membranes is reviewed with the goal of gaining insight into the evolution of membrane proteins. topics include: translocon-dependent membrane protein insertion, antibiotic ...	2009	20039094
helix insertion into bilayers and the evolution of membrane proteins.	polytopic alpha-helical membrane proteins cannot spontaneously insert into lipid bilayers without assistance from polytopic alpha-helical membrane proteins that already reside in the membrane. this raises the question of how these proteins evolved. our current knowledge of the insertion of alpha-helices into natural and model membranes is reviewed with the goal of gaining insight into the evolution of membrane proteins. topics include: translocon-dependent membrane protein insertion, antibiotic ...	2009	20039094
the adenosine wedge: a new structural motif in ribosomal rna.	here, we present a new recurrent rna arrangement, the so-called adenosine wedge (a-wedge), which is found in three places of the ribosomal rna in both ribosomal subunits. the arrangement has a hierarchical structure, consisting of elements previously described as recurrent motifs, namely, the along-groove packing motif, the a-minor and the hook-turn. within the a-wedge, these elements are involved in different types of cause-effect relationships, providing together for the particular tertiary st ...	2010	20038632
accommodation of tmrna-smpb into stalled ribosomes: a cryo-em study.	in eubacteria, translation of defective messenger rnas (mrnas) produces truncated polypeptides that stall on the ribosome. a quality control mechanism referred to as trans-translation is performed by transfer-messenger rna (tmrna), a specialized rna acting as both a trna and an mrna, associated with small protein b (smpb). so far, a clear view of the structural movements of both the protein and rna necessary to perform accommodation is still lacking. by using a construct containing the trna-like ...	2010	20038631
structural motifs of the bacterial ribosomal proteins s20, s18 and s16 that contact rrna present in the eukaryotic ribosomal proteins s25, s26 and s27a, respectively.	the majority of constitutive proteins in the bacterial 30s ribosomal subunit have orthologues in eukarya and archaea. the eukaryotic counterparts for the remainder (s6, s16, s18 and s20) have not been identified. we assumed that amino acid residues in the ribosomal proteins that contact rrna are to be constrained in evolution and that the most highly conserved of them are those residues that are involved in forming the secondary protein structure. we aligned the sequences of the bacterial riboso ...	2010	20034956
polymorphisms associated with resistance and cross-resistance to aminoglycosides and capreomycin in mycobacterium tuberculosis isolates from south korean patients with drug-resistant tuberculosis.	the aminoglycosides streptomycin, amikacin, and kanamycin and the cyclic polypeptide capreomycin are all widely used in second-line therapy for patients who develop multidrug-resistant tuberculosis. we have characterized a set of 106 clinical isolates of mycobacterium tuberculosis using phenotypic drug susceptibility testing (dst) to determine the extent of resistance to each agent and cross-resistance between agents. these results were compared with polymorphisms in the dna sequences of ribosom ...	2010	20032248
polymorphisms associated with resistance and cross-resistance to aminoglycosides and capreomycin in mycobacterium tuberculosis isolates from south korean patients with drug-resistant tuberculosis.	the aminoglycosides streptomycin, amikacin, and kanamycin and the cyclic polypeptide capreomycin are all widely used in second-line therapy for patients who develop multidrug-resistant tuberculosis. we have characterized a set of 106 clinical isolates of mycobacterium tuberculosis using phenotypic drug susceptibility testing (dst) to determine the extent of resistance to each agent and cross-resistance between agents. these results were compared with polymorphisms in the dna sequences of ribosom ...	2010	20032248
the oxidative dna glycosylases of mycobacterium tuberculosis exhibit different substrate preferences from their escherichia coli counterparts.	the dna glycosylases that remove oxidized dna bases fall into two general families: the fpg/nei family and the nth superfamily. based on protein sequence alignments, we identified four putative fpg/nei family members, as well as a putative nth protein in mycobacterium tuberculosis h37rv. all four fpg/nei proteins were successfully overexpressed using a bicistronic vector created in our laboratory. the mtunth protein was also overexpressed in soluble form. the substrate specificities of the purif ...	2010	20031487
the oxidative dna glycosylases of mycobacterium tuberculosis exhibit different substrate preferences from their escherichia coli counterparts.	the dna glycosylases that remove oxidized dna bases fall into two general families: the fpg/nei family and the nth superfamily. based on protein sequence alignments, we identified four putative fpg/nei family members, as well as a putative nth protein in mycobacterium tuberculosis h37rv. all four fpg/nei proteins were successfully overexpressed using a bicistronic vector created in our laboratory. the mtunth protein was also overexpressed in soluble form. the substrate specificities of the purif ...	2010	20031487
reductive coupling of nitrogen monoxide (*no) facilitated by heme/copper complexes.	the interactions of nitrogen monoxide (no; nitric oxide) with transition metal centers continue to be of great interest, in part due to their importance in biochemical processes. here, we describe no((g)) reductive coupling chemistry of possible relevance to that process (i.e., nitric oxide reductase (nor) biochemistry), which occurs at the heme/cu active site of cytochrome c oxidases (ccos). in this report, heme/cu/*no((g)) activity is studied using 1:1 ratios of heme and copper complex compo ...	2010	20030370
the pseudomonas aeruginosa magnesium transporter mgte inhibits transcription of the type iii secretion system.	pseudomonas aeruginosa is an opportunistic pathogen that causes life-long pneumonia in individuals with cystic fibrosis (cf). these long-term infections are maintained by bacterial biofilm formation in the cf lung. we have recently developed a model of p. aeruginosa biofilm formation on cultured cf airway epithelial cells. using this model, we discovered that mutation of a putative magnesium transporter gene, called mgte, led to increased cytotoxicity of p. aeruginosa toward epithelial cells. th ...	2010	20028803
the pseudomonas aeruginosa magnesium transporter mgte inhibits transcription of the type iii secretion system.	pseudomonas aeruginosa is an opportunistic pathogen that causes life-long pneumonia in individuals with cystic fibrosis (cf). these long-term infections are maintained by bacterial biofilm formation in the cf lung. we have recently developed a model of p. aeruginosa biofilm formation on cultured cf airway epithelial cells. using this model, we discovered that mutation of a putative magnesium transporter gene, called mgte, led to increased cytotoxicity of p. aeruginosa toward epithelial cells. th ...	2010	20028803
amyloidogenic sequences in native protein structures.	numerous short peptides have been shown to form beta-sheet amyloid aggregates in vitro. proteins that contain such sequences are likely to be problematic for a cell, due to their potential to aggregate into toxic structures. we investigated the structures of 30 proteins containing 45 sequences known to form amyloid, to see how the proteins cope with the presence of these potentially toxic sequences, studying secondary structure, hydrogen-bonding, solvent accessible surface area and hydrophobicit ...	2009	20027621
amyloidogenic sequences in native protein structures.	numerous short peptides have been shown to form beta-sheet amyloid aggregates in vitro. proteins that contain such sequences are likely to be problematic for a cell, due to their potential to aggregate into toxic structures. we investigated the structures of 30 proteins containing 45 sequences known to form amyloid, to see how the proteins cope with the presence of these potentially toxic sequences, studying secondary structure, hydrogen-bonding, solvent accessible surface area and hydrophobicit ...	2009	20027621
dissecting the role of critical residues and substrate preference of a fatty acyl-coa synthetase (fadd13) of mycobacterium tuberculosis.	newly emerging multi-drug resistant strains of mycobacterium tuberculosis (m.tb) severely limit the treatment options for tuberculosis (tb); hence, new antitubercular drugs are urgently needed. the myma operon is essential for the virulence and intracellular survival of m.tb and thus represents an attractive target for the development of new antitubercular drugs. this study is focused on the structure-function relationship of fatty acyl-coa synthetase (fadd13, rv3089) belonging to the myma opero ...	2009	20027301