Publications

comparison of fungal 80 s ribosomes by cryo-em reveals diversity in structure and conformation of rrna expansion segments.	compared to the prokaryotic 70 s ribosome, the eukaryotic 80 s ribosome contains additional ribosomal proteins and extra segments of rrna, referred to as rrna expansion segments (es). these eukaryotic-specific rrna es are mainly on the periphery of the 80 s ribosome, as revealed by cryo-electron microscopy (cryo-em) studies, but their precise function is not known. to address the question of whether the rrna es are structurally conserved among 80 s ribosomes of different fungi we performed cryo- ...	2007	17434183
high-throughput identification of inhibitors of human mitochondrial peptide deformylase.	the human mitochondrial peptide deformylase (hspdf) provides a potential new target for broadly acting antiproliferative agents. to identify novel nonpeptidomimetic and nonhydroxamic acid-based inhibitors of hspdf, the authors have developed a high-throughput screening (hts) strategy using a fluorescence polarization (fp)-based binding assay as the primary assay for screening chemical libraries, followed by an enzymatic-based assay to confirm hits, prior to characterization of their antiprolifer ...	2007	17435169
analysis of the assembly profiles for mitochondrial- and nuclear-dna-encoded subunits into complex i.	complex i of the respiratory chain is composed of at least 45 subunits that assemble together at the mitochondrial inner membrane. defects in human complex i result in energy generation disorders and are also implicated in parkinson's disease and altered apoptotic signaling. the assembly of this complex is poorly understood and is complicated by its large size and its regulation by two genomes, with seven subunits encoded by mitochondrial dna (mtdna) and the remainder encoded by nuclear genes. h ...	2007	17438127
site-specific s-glutathiolation of mitochondrial nadh ubiquinone reductase.	the generation of reactive oxygen species in mitochondria acts as a redox signal in triggering cellular events such as apoptosis, proliferation, and senescence. overproduction of superoxide (o2-) and o2--derived oxidants changes the redox status of the mitochondrial gsh pool. an electron transport protein, mitochondrial complex i, is the major host of reactive/regulatory protein thiols. an important response of protein thiols to oxidative stress is to reversibly form protein mixed disulfide vi ...	2007	17444656
structures of modified eef2 80s ribosome complexes reveal the role of gtp hydrolysis in translocation.	on the basis of kinetic data on ribosome protein synthesis, the mechanical energy for translocation of the mrna-trna complex is thought to be provided by gtp hydrolysis of an elongation factor (eef2 in eukaryotes, ef-g in bacteria). we have obtained cryo-em reconstructions of eukaryotic ribosomes complexed with adp-ribosylated eef2 (adpr-eef2), before and after gtp hydrolysis, providing a structural basis for analyzing the gtpase-coupled mechanism of translocation. using the adp-ribosyl group as ...	2007	17446867
enzymology and evolution of the pyruvate pathway to 2-oxobutyrate in methanocaldococcus jannaschii.	the archaeon methanocaldococcus jannaschii uses three different 2-oxoacid elongation pathways, which extend the chain length of precursors in leucine, isoleucine, and coenzyme b biosyntheses. in each of these pathways an aconitase-type hydrolyase catalyzes an hydroxyacid isomerization reaction. the genome sequence of m. jannaschii encodes two homologs of each large and small subunit that forms the hydrolyase, but the genes are not cotranscribed. the genes are more similar to each other than to p ...	2007	17449626
the 51-63 base pair of trna confers specificity for binding by ef-tu.	elongation factor tu (ef-tu) exhibits significant specificity for the different elongator trna bodies in order to offset its variable affinity to the esterified amino acid. three x-ray cocrystal structures reveal that while most of the contacts with the protein involve the phosphodiester backbone of trna, a single hydrogen bond is observed between the glu390 and the amino group of a guanine in the 51-63 base pair in the t-stem of trna. here we show that the glu390ala mutation of thermus thermoph ...	2007	17449728
mechanism for the ttdnaa-tt-oric cooperative interaction at high temperature and duplex opening at an unusual at-rich region in thermoanaerobacter tengcongensis.	thermoanaerobacter tengcongensis is an anaerobic low-gc thermophilic bacterium. to further elucidate the replication initiation of chromosomal dna at high temperature, the interaction between the replication initiator (ttdnaa) and the putative origin (tt-oric) in this thermophile was investigated. we found that efficient binding of ttdnaa to tt-oric at high temperature requires (i) at least two neighboring dnaa boxes, (ii) the specific feature of the ttdnaa domain iv and (iii) the self-oligomeri ...	2007	17452366
the outer membrane secretin pilq from neisseria meningitidis binds dna.	neisseria meningitidis is naturally competent for transformation throughout its growth cycle. transformation in neisserial species is coupled to the expression of type iv pili, which are present on the cell surface as bundled filamentous appendages, and are assembled, extruded and retracted by the pilus biogenesis components. during the initial phase of the transformation process, binding and uptake of dna takes place with entry through a presumed outer-membrane channel into the periplasm. this ...	2007	17464074
real-time footprinting of dna in the first kinetically significant intermediate in open complex formation by escherichia coli rna polymerase.	the architecture of cellular rna polymerases (rnaps) dictates that transcription can begin only after promoter dna bends into a deep channel and the start site nucleotide (+1) binds in the active site located on the channel floor. formation of this transcriptionally competent "open" complex (rp(o)) by escherichia coli rnap at the lambdap(r) promoter is greatly accelerated by dna upstream of base pair -47 (with respect to +1). here we report real-time hydroxyl radical (*oh) and potassium permanga ...	2007	17470797
post-transcriptional modification mapping in the clostridium acetobutylicum 16s rrna by mass spectrometry and reverse transcriptase assays.	post-transcriptional modifications in ribosomal rna are believed to fine-tune the rna functions. the present study describes the characterization of the post-transcriptional modifications in clostridium acetobutylicum 16s rrna, using high-pressure liquid chromatography (hplc) coupled to electrospray ionization mass spectrometry and reverse transcriptase assays. the combination of these techniques allowed the identification of eleven modified nucleosides, which were mapped onto the rrna sequence. ...	2007	17478509
structural elements defining elongation factor tu mediated suppression of codon ambiguity.	in most prokaryotes asn-trna(asn) and gln-trna(gln) are formed by amidation of aspartate and glutamate mischarged onto trna(asn) and trna(gln), respectively. coexistence in the organism of mischarged asp-trna(asn) and glu-trna(gln) and the homologous asn-trna(asn) and gln-trna(gln) does not, however, lead to erroneous incorporation of asp and glu into proteins, since ef-tu discriminates the misacylated trnas from the correctly charged ones. this property contrasts with the canonical function of ...	2007	17478519
fine-tuning of translation termination efficiency in saccharomyces cerevisiae involves two factors in close proximity to the exit tunnel of the ribosome.	in eukaryotes, release factors 1 and 3 (erf1 and erf3) are recruited to promote translation termination when a stop codon on the mrna enters at the ribosomal a-site. however, their overexpression increases termination efficiency only moderately, suggesting that other factors might be involved in the termination process. to determine such unknown components, we performed a genetic screen in saccharomyces cerevisiae that identified genes increasing termination efficiency when overexpressed. for th ...	2007	17483428
structural basis for functional mimicry of long-variable-arm trna by transfer-messenger rna.	tmrna and small protein b (smpb) are essential trans-translation system components. in the present study, we determined the crystal structure of smpb in complex with the entire trna domain of the tmrna from thermus thermophilus. overall, the ribonucleoprotein complex (trnp) mimics a long-variable-arm trna (class ii trna) in the canonical l-shaped tertiary structure. the tmrna terminus corresponds to the acceptor and t arms, or the upper part, of trna. on the other hand, the smpb protein simulate ...	2007	17488812
identification of the biosynthetic gene cluster and an additional gene for resistance to the antituberculosis drug capreomycin.	capreomycin (cmn) belongs to the tuberactinomycin family of nonribosomal peptide antibiotics that are essential components of the drug arsenal for the treatment of multidrug-resistant tuberculosis. members of this antibiotic family target the ribosomes of sensitive bacteria and disrupt the function of both subunits of the ribosome. resistance to these antibiotics in mycobacterium species arises due to mutations in the genes coding for the 16s or 23s rrna but can also arise due to mutations in a ...	2007	17496129
agrobacterium para/mind-like virc1 spatially coordinates early conjugative dna transfer reactions.	agrobacterium tumefaciens translocates t-dna through a polar virb/d4 type iv secretion (t4s) system. virc1, a factor required for efficient t-dna transfer, bears a deviant walker a and other sequence motifs characteristic of para and mind atpases. here, we show that virc1 promotes conjugative t-dna transfer by stimulating generation of multiple copies per cell of the t-dna substrate (t-complex) through pairwise interactions with the processing factors vird2 relaxase, virc2, and vird1. virc1 also ...	2007	17505518
cross-linked seca dimers are not functional in protein translocation.	the atpase seca is involved in post-translational protein translocation through the secy channel across the bacterial inner membrane. seca is a dimer that can dissociate into monomers with translocation activity. here, we have addressed whether dissociation of the seca dimer is required for translocation. we show that a dimer in which the two subunits are cross-linked by disulfide bridges is inactive in protein translocation, translocation atpase, and binding to a lipid bilayer. in contrast, upo ...	2007	17511989
rna chaperone activity of l1 ribosomal proteins: phylogenetic conservation and splicing inhibition.	rna chaperone activity is defined as the ability of proteins to either prevent rna from misfolding or to open up misfolded rna conformations. one-third of all large ribosomal subunit proteins from e. coli display this activity, with l1 exhibiting one of the highest activities. here, we demonstrate via the use of in vitro trans- and cis-splicing assays that the rna chaperone activity of l1 is conserved in all three domains of life. however, thermophilic archaeal l1 proteins do not display rna cha ...	2007	17517772
developing limited proteolysis and mass spectrometry for the characterization of ribosome topography.	an approach that combines limited proteolysis and matrix-assisted laser desorption/ionization mass spectrometry (maldi-ms) has been developed to probe protease-accessible sites of ribosomal proteins from intact ribosomes. escherichia coli and thermus thermophilus 70s ribosomes were subjected to limited proteolysis using different proteases under strictly controlled conditions. intact ribosomal proteins and large proteolytic peptides were recovered and directly analyzed by maldi-ms, which allows ...	2007	17521915
interactions between the lipoprotein pilp and the secretin pilq in neisseria meningitidis.	neisseria meningitidis can be the causative agent of meningitis or septicemia. this bacterium expresses type iv pili, which mediate a variety of functions, including autoagglutination, twitching motility, biofilm formation, adherence, and dna uptake during transformation. the secretin pilq supports type iv pilus extrusion and retraction, but it also requires auxiliary proteins for its assembly and localization in the outer membrane. here we have studied the physical properties of the lipoprotein ...	2007	17526700
prediction of functional sites based on the fuzzy oil drop model.	a description of many biological processes requires knowledge of the 3-d structure of proteins and, in particular, the defined active site responsible for biological function. many proteins, the genes of which have been identified as the result of human genome sequencing, and which were synthesized experimentally, await identification of their biological activity. currently used methods do not always yield satisfactory results, and new algorithms need to be developed to recognize the localizatio ...	2007	17530916
the first agmatine/cadaverine aminopropyl transferase: biochemical and structural characterization of an enzyme involved in polyamine biosynthesis in the hyperthermophilic archaeon pyrococcus furiosus.	we report here the characterization of the first agmatine/cadaverine aminopropyl transferase (acapt), the enzyme responsible for polyamine biosynthesis from an archaeon. the gene pf0127 encoding acapt in the hyperthermophile pyrococcus furiosus was cloned and expressed in escherichia coli, and the recombinant protein was purified to homogeneity. p. furiosus acapt is a homodimer of 65 kda. the broad substrate specificity of the enzyme toward the amine acceptors is unique, as agmatine, 1,3-diamino ...	2007	17545282
collaboration between the clpb aaa+ remodeling protein and the dnak chaperone system.	clpb and hsp104, members of the aaa+ superfamily of proteins, protect cells from the devastating effects of protein inactivation and aggregation that arise after extreme heat stress. they exist as a hexameric ring and contain two nucleotide-binding sites per monomer. clpb and hsp104 are able to dissolve protein aggregates in conjunction with the dnak/hsp70 chaperone system, although the roles of the individual chaperones in disaggregation are not well understood. in the absence of the dnak/hsp70 ...	2007	17545305
long-range structural effects of a charcot-marie-tooth disease-causing mutation in human glycyl-trna synthetase.	functional expansion of specific trna synthetases in higher organisms is well documented. these additional functions may explain why dominant mutations in glycyl-trna synthetase (glyrs) and tyrosyl-trna synthetase cause charcot-marie-tooth (cmt) disease, the most common heritable disease of the peripheral nervous system. at least 10 disease-causing mutant alleles of glyrs have been annotated. these mutations scatter broadly across the primary sequence and have no apparent unifying connection. he ...	2007	17545306
new insights into the binding mode of coenzymes: structure of thermus thermophilus delta1-pyrroline-5-carboxylate dehydrogenase complexed with nadp+.	delta(1)-pyrroline-5-carboxylate dehydrogenase (p5cdh) is known to preferentially use nad(+) as a coenzyme. the k(cat) value of thermus thermophilus p5cdh (ttp5cdh) is four times lower for nadp(+) than for nad(+). the crystal structure of nadp(+)-bound ttp5cdh was solved in order to study the structure-activity relationships for the coenzymes. the binding mode of nadp(+) is essentially identical to that in the previously solved nad(+)-bound form, except for the regions around the additional 2'-p ...	2007	17554163
expression, purification, assay, and crystal structure of perdeuterated human arginase i.	arginase is a manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to yield l-ornithine and urea. in order to establish a foundation for future neutron diffraction studies that will provide conclusive structural information regarding proton/deuteron positions in enzyme-inhibitor complexes, we have expressed, purified, assayed, and determined the x-ray crystal structure of perdeuterated (i.e., fully deuterated) human arginase i complexed with 2(s)-amino-6-boronohexanoic acid (abh) ...	2007	17562323
structural basis for recruitment of tandem hotdog domains in acyl-coa thioesterase 7 and its role in inflammation.	acyl-coa thioesterases (acots) catalyze the hydrolysis of fatty acyl-coa to free fatty acid and coa and thereby regulate lipid metabolism and cellular signaling. we present a comprehensive structural and functional characterization of mouse acyl-coa thioesterase 7 (acot7). whereas prokaryotic homologues possess a single thioesterase domain, mammalian acot7 contains a pair of domains in tandem. we determined the crystal structures of both the n- and c-terminal domains of the mouse enzyme, and inf ...	2007	17563367
cloning, expression, purification, crystallization and preliminary x-ray analysis of thermus aquaticus succinyl-coa synthetase.	succinyl-coa synthetase (scs) is an enzyme of the citric acid cycle and is thus found in most species. to date, there are no structures available of scs from a thermophilic organism. to investigate how the enzyme adapts to higher temperatures, scs from thermus aquaticus was cloned, overexpressed, purified and crystallized. attempts to crystallize the enzyme were thwarted by proteolysis of the beta-subunit and preferential crystallization of the truncated form. crystals of full-length scs were gr ...	2007	17565180
preliminary x-ray crystallographic study of glucose dehydrogenase from thermus thermophilus hb8.	thermus thermophilus is an aerobic chemoorganotroph that has been found to grow anaerobically in the presence of nitrate. crystals of glucose dehydrogenase (gdh) from t. thermophilus hb8 belong to space group p2(1), with unit-cell parameters a = 36.90, b = 132.96, c = 60.78 a, beta = 97.2 degrees. preliminary studies and molecular-replacement calculations reveal that the asymmetric unit contains two monomers.	2007	17565193
crystal structure of saccharomyces cerevisiae 6-phosphogluconate dehydrogenase gnd1.	as the third enzyme of the pentose phosphate pathway, 6-phosphogluconate dehydrogenase (6pgdh) is the main generator of cellular nadph. both thioredoxin reductase and glutathione reductase require nadph as the electron donor to reduce oxidized thioredoxin or glutathione (gssg). since thioredoxin and gsh are important antioxidants, it is not surprising that 6pgdh plays a critical role in protecting cells from oxidative stress. furthermore the activity of 6pgdh is associated with several human dis ...	2007	17570834
structural basis for recognition of cognate trna by tyrosyl-trna synthetase from three kingdoms.	the specific aminoacylation of trna by tyrosyl-trna synthetases (tyrrss) relies on the identity determinants in the cognate trna(tyr)s. we have determined the crystal structure of saccharomyces cerevisiae tyrrs (scetyrrs) complexed with a tyr-amp analog and the native trna(tyr)(gpsia). structural information for tyrrs-trna(tyr) complexes is now full-line for three kingdoms. because the archaeal/eukaryotic tyrrss-trna(tyr)s pairs do not cross-react with their bacterial counterparts, the recogniti ...	2007	17576676
a loop loop interaction and a k-turn motif located in the lysine aptamer domain are important for the riboswitch gene regulation control.	the lysine riboswitch is associated to the lysc gene in bacillus subtilis, and the binding of lysine modulates the rna structure to allow the formation of an intrinsic terminator presumably involved in transcription attenuation. the complex secondary structure of the lysine riboswitch aptamer is organized around a five-way junction that undergoes structural changes upon ligand binding. using single-round transcription assays, we show that a loop-loop interaction is important for lysine-induced t ...	2007	17585050
characterization and mechanistic studies of type ii isopentenyl diphosphate:dimethylallyl diphosphate isomerase from staphylococcus aureus.	the recently identified type ii isopentenyl diphosphate (ipp):dimethylallyl diphosphate (dmapp) isomerase (idi-2) is a flavoenzyme that requires fmn and nad(p)h for activity. idi-2 is an essential enzyme for the biosynthesis of isoprenoids in several pathogenic bacteria including staphylococcus aureus, streptococcus pneumoniae, and enterococcus faecalis, and thus is considered as a potential new drug target to battle bacterial infections. one notable feature of the idi-2 reaction is that there i ...	2007	17585782
protein aq_1862 from the hyperthermophilic bacterium aquifex aeolicus is a porin and contains two conductance pathways of different selectivity.	the "hypothetical protein" aq_1862 was isolated from the membrane fraction of aquifex aeolicus and identified as the major porin. in experiments with one conducting unit (molecule) a conductance of 1.4 ns was observed in 0.1 m kcl at ph 7.5. this stable (basic) conductance was superimposed by conductance fluctuations of approximately 0.25 ns. because both events were always observed simultaneously, it is suggested that they are caused by the same molecular entity. nonetheless they show very diff ...	2007	17586565
the 2.2 a resolution crystal structure of bacillus cereus nif3-family protein yqfo reveals a conserved dimetal-binding motif and a regulatory domain.	yqfo of bacillus cereus is a member of the widespread nif3 family of proteins, which has been highlighted as an important target for structural genomics. the n- and c-terminal domains are conserved across the family and contain a dimetal-binding motif in a putative active site. yqfo contains an insert in the middle of the protein, present in a minority of bacterial family members. the structure of yqfo was determined at a resolution of 2.2 a and reveals conservation of the putative active site. ...	2007	17586767
crystal structures of tm0549 and ne1324--two orthologs of e. coli ahas isozyme iii small regulatory subunit.	crystal structures of two orthologs of the regulatory subunit of acetohydroxyacid synthase iii (ahas, ec 2.2.1.6) from thermotoga maritima (tm0549) and nitrosomonas europea (ne1324) were determined by single-wavelength anomalous diffraction methods with the use of selenomethionine derivatives at 2.3 a and 2.5 a, respectively. tm0549 and ne1324 share the same fold, and in both proteins the polypeptide chain contains two separate domains of a similar size. each protein contains a c-terminal domain ...	2007	17586771
direct localization of the 51 and 24 kda subunits of mitochondrial complex i by three-dimensional difference imaging.	complex i is the largest complex in the respiratory chain, and the least understood. we have determined the 3d structure of complex i from yarrowia lipolytica lacking the flavoprotein part of the n-module, which consists of the 51 kda (nubm) and the 24 kda (nuhm) subunits. the reconstruction was determined by 3d electron microscopy of single particles. a comparison to our earlier reconstruction of the complete y. lipolytica complex i clearly assigns the two flavoprotein subunits to an outer lobe ...	2007	17591445
testing constraints on rrna bases that make nonsequence-specific contacts with the codon-anticodon complex in the ribosomal a site.	during protein synthesis, interactions between the decoding center of the ribosome and the codon-anticodon complexes maintain translation accuracy. correct aminoacyl-trnas induce the ribosome to shift into a "closed" conformation that both blocks trna dissociation and accelerates the process of trna acceptance. as part of the ribosomal recognition of cognate trnas, the rrna nucleotides g530 and a1492 form a hydrogen-bonded pair that interacts with the middle position of the codon.anticodon compl ...	2007	17592040
geranylgeranyl diphosphate synthase in fission yeast is a heteromer of farnesyl diphosphate synthase (fps), fps1, and an fps-like protein, spo9, essential for sporulation.	both farnesyl diphosphate synthase (fps) and geranylgeranyl diphosphate synthase (ggps) are key enzymes in the synthesis of various isoprenoid-containing compounds and proteins. here, we describe two novel schizosaccharomyces pombe genes, fps1(+) and spo9(+), whose products are similar to fps in primary structure, but whose functions differ from one another. fps1 is essential for vegetative growth, whereas, a spo9 null mutant exhibits temperature-sensitive growth. expression of fps1(+), but not ...	2007	17596513
genome evolution and the emergence of fruiting body development in myxococcus xanthus.	lateral gene transfer (lgt) is thought to promote speciation in bacteria, though well-defined examples have not been put forward.	2007	18159227
oligomeric states of the seca and secyeg core components of the bacterial sec translocon.	many proteins synthesized in the cytoplasm ultimately function in non-cytoplasmic locations. in escherichia coli, the general secretory (sec) pathway transports the vast majority of these proteins. two fundamental components of the sec transport pathway are the secyeg heterotrimeric complex that forms the channel through the cytoplasmic membrane, and seca, the atpase that drives the preprotein to and across the membrane. this review focuses on what is known about the oligomeric states of these c ...	2007	17011510
oligomeric states of the seca and secyeg core components of the bacterial sec translocon.	many proteins synthesized in the cytoplasm ultimately function in non-cytoplasmic locations. in escherichia coli, the general secretory (sec) pathway transports the vast majority of these proteins. two fundamental components of the sec transport pathway are the secyeg heterotrimeric complex that forms the channel through the cytoplasmic membrane, and seca, the atpase that drives the preprotein to and across the membrane. this review focuses on what is known about the oligomeric states of these c ...	2007	17011510
coordinate expression of the acetyl coenzyme a carboxylase genes, accb and accc, is necessary for normal regulation of biotin synthesis in escherichia coli.	transcription of the biotin (bio) biosynthetic operon of escherichia coli is negatively regulated by the bira protein, an atypical repressor protein in that it is also an enzyme. the bira-catalyzed reaction involves the covalent attachment of biotin to accb, a subunit of acetyl coenzyme (acetyl-coa) carboxylase. the two functions of bira allow regulation of the bio operon to respond to the intracellular concentrations of both biotin and unbiotinylated accb. we report here that bio operon express ...	2007	17056747
coordinate expression of the acetyl coenzyme a carboxylase genes, accb and accc, is necessary for normal regulation of biotin synthesis in escherichia coli.	transcription of the biotin (bio) biosynthetic operon of escherichia coli is negatively regulated by the bira protein, an atypical repressor protein in that it is also an enzyme. the bira-catalyzed reaction involves the covalent attachment of biotin to accb, a subunit of acetyl coenzyme (acetyl-coa) carboxylase. the two functions of bira allow regulation of the bio operon to respond to the intracellular concentrations of both biotin and unbiotinylated accb. we report here that bio operon express ...	2007	17056747
carotenoid biosynthesis in the primitive red alga cyanidioschyzon merolae.	cyanidioschyzon merolae is considered to be one of the most primitive of eukaryotic photosynthetic organisms. to obtain insights into the origin and evolution of the pathway of carotenoid biosynthesis in eukaryotic plants, the carotenoid content of c. merolae was ascertained, genes encoding enzymes of carotenoid biosynthesis in this unicellular red alga were identified, and the activities of two candidate pathway enzymes of particular interest, lycopene cyclase and beta-carotene hydroxylase, wer ...	2007	17085635
carotenoid biosynthesis in the primitive red alga cyanidioschyzon merolae.	cyanidioschyzon merolae is considered to be one of the most primitive of eukaryotic photosynthetic organisms. to obtain insights into the origin and evolution of the pathway of carotenoid biosynthesis in eukaryotic plants, the carotenoid content of c. merolae was ascertained, genes encoding enzymes of carotenoid biosynthesis in this unicellular red alga were identified, and the activities of two candidate pathway enzymes of particular interest, lycopene cyclase and beta-carotene hydroxylase, wer ...	2007	17085635
structural and biochemical characterization of human orphan dhrs10 reveals a novel cytosolic enzyme with steroid dehydrogenase activity.	to this day, a significant proportion of the human genome remains devoid of functional characterization. in this study, we present evidence that the previously functionally uncharacterized product of the human dhrs10 gene is endowed with 17beta-hsd (17beta-hydroxysteroid dehydrogenase) activity. 17beta-hsd enzymes are primarily involved in the metabolism of steroids at the c-17 position and also of other substrates such as fatty acids, prostaglandins and xenobiotics. in vitro, dhrs10 converts na ...	2007	17067289
biosynthesis of phosphoserine in the methanococcales.	methanococcus maripaludis and methanocaldococcus jannaschii produce cysteine for protein synthesis using a trna-dependent pathway. these methanogens charge trna(cys) with l-phosphoserine, which is also an intermediate in the predicted pathways for serine and cystathionine biosynthesis. to establish the mode of phosphoserine production in methanococcales, cell extracts of m. maripaludis were shown to have phosphoglycerate dehydrogenase and phosphoserine aminotransferase activities. the heterologo ...	2007	17071763
biosynthesis of phosphoserine in the methanococcales.	methanococcus maripaludis and methanocaldococcus jannaschii produce cysteine for protein synthesis using a trna-dependent pathway. these methanogens charge trna(cys) with l-phosphoserine, which is also an intermediate in the predicted pathways for serine and cystathionine biosynthesis. to establish the mode of phosphoserine production in methanococcales, cell extracts of m. maripaludis were shown to have phosphoglycerate dehydrogenase and phosphoserine aminotransferase activities. the heterologo ...	2007	17071763
similarity search for local protein structures at atomic resolution by exploiting a database management system.	a method to search for local structural similarities in proteins at atomic resolution is presented. it is demonstrated that a huge amount of structural data can be handled within a reasonable cpu time by using a conventional relational database management system with appropriate indexing of geometric data. this method, which we call geometric indexing, can enumerate ligand binding sites that are structurally similar to sub-structures of a query protein among more than 160,000 possible candidates ...	2007	27857569
bis{μ-2,2'-[1,1'-(ethane-1,2-diyldinitrilo)diethyl-idyne]diphenolato}bis-[(benzoato-κo)manganese(iii)] dihydrate.	the title compound, [mn(2)(c(18)h(18)n(2)o(2))(2)(c(7)h(5)o(2))(2)]·2h(2)o, was synthesized by the reaction between manganese(ii) benzoate and the schiff base generated in situ by the condensation of ethane-1,2-diamine and o-hydroxy-aceto-phen-one. the jahn-teller-distorted manganese(iii) ions of the centrosymmetric dimer are connected through phen-oxy bridges. hydrogen-bonding inter-actions between the uncoord-in-ated c=o of the benzoate and uncoordinated water mol-ecules link the dimers into a ...	2007	21200504
bis{μ-2,2'-[1,1'-(ethane-1,2-diyldinitrilo)diethyl-idyne]diphenolato}bis-[(benzoato-κo)manganese(iii)] dihydrate.	the title compound, [mn(2)(c(18)h(18)n(2)o(2))(2)(c(7)h(5)o(2))(2)]·2h(2)o, was synthesized by the reaction between manganese(ii) benzoate and the schiff base generated in situ by the condensation of ethane-1,2-diamine and o-hydroxy-aceto-phen-one. the jahn-teller-distorted manganese(iii) ions of the centrosymmetric dimer are connected through phen-oxy bridges. hydrogen-bonding inter-actions between the uncoord-in-ated c=o of the benzoate and uncoordinated water mol-ecules link the dimers into a ...	2007	21200504
the ins and outs of translation.		2007	18086326
thiostrepton inhibition of trna delivery to the ribosome.	ribosome-stimulated hydrolysis of guanosine-5'-triphosphate (gtp) by guanosine triphosphatase (gtpase) translation factors drives protein synthesis by the ribosome. allosteric coupling of gtp hydrolysis by elongation factor tu (ef-tu) at the ribosomal gtpase center to messenger rna (mrna) codon:aminoacyl-transfer rna (aa-trna) anticodon recognition at the ribosomal decoding site is essential for accurate and rapid aa-trna selection. here we use single-molecule methods to investigate the mechanis ...	2007	17951333
clusters of orthologous genes for 41 archaeal genomes and implications for evolutionary genomics of archaea.	an evolutionary classification of genes from sequenced genomes that distinguishes between orthologs and paralogs is indispensable for genome annotation and evolutionary reconstruction. shortly after multiple genome sequences of bacteria, archaea, and unicellular eukaryotes became available, an attempt on such a classification was implemented in clusters of orthologous groups of proteins (cogs). rapid accumulation of genome sequences creates opportunities for refining cogs but also represents a c ...	2007	18042280
cryo-em study of the spinach chloroplast ribosome reveals the structural and functional roles of plastid-specific ribosomal proteins.	protein synthesis in the chloroplast is carried out by chloroplast ribosomes (chloro-ribosome) and regulated in a light-dependent manner. chloroplast or plastid ribosomal proteins (prps) generally are larger than their bacterial counterparts, and chloro-ribosomes contain additional plastid-specific ribosomal proteins (psrps); however, it is unclear to what extent these proteins play structural or regulatory roles during translation. we have obtained a three-dimensional cryo-em map of the spinach ...	2007	18042701
protein crystallography for non-crystallographers, or how to get the best (but not more) from published macromolecular structures.	the number of macromolecular structures deposited in the protein data bank now exceeds 45,000, with the vast majority determined using crystallographic methods. thousands of studies describing such structures have been published in the scientific literature, and 14 nobel prizes in chemistry or medicine have been awarded to protein crystallographers. as important as these structures are for understanding the processes that take place in living organisms and also for practical applications such as ...	2007	18034855
protein crystallography for non-crystallographers, or how to get the best (but not more) from published macromolecular structures.	the number of macromolecular structures deposited in the protein data bank now exceeds 45,000, with the vast majority determined using crystallographic methods. thousands of studies describing such structures have been published in the scientific literature, and 14 nobel prizes in chemistry or medicine have been awarded to protein crystallographers. as important as these structures are for understanding the processes that take place in living organisms and also for practical applications such as ...	2007	18034855
simple fluorescent sensors engineered with catalytic dna 'mgz' based on a non-classic allosteric design.	most nae (nucleic acid enzyme) sensors are composed of an rna-cleaving catalytic motif and an aptameric receptor. they operate by activating or repressing the catalytic activity of a relevant nae through the conformational change in the aptamer upon target binding. to transduce a molecular recognition event to a fluorescence signal, a fluorophore-quencher pair is attached to opposite ends of the rna substrate such that when the nae cleaves the substrate, an increased level of fluorescence can be ...	2007	18030352
a comprehensive analysis of non-sequential alignments between all protein structures.	the majority of relations between proteins can be represented as a conventional sequential alignment. nevertheless, unusual non-sequential alignments with different connectivity of the aligned fragments in compared proteins have been reported by many researchers. it is interesting to understand those non-sequential alignments; are they unique, sporadic cases or they occur frequently; do they belong to a few specific folds or spread among many different folds, as a common feature of protein struc ...	2007	18005453
structural basis for signal-sequence recognition by the translocase motor seca as determined by nmr.	recognition of signal sequences by cognate receptors controls the entry of virtually all proteins to export pathways. despite its importance, this process remains poorly understood. here, we present the solution structure of a signal peptide bound to seca, the 204 kda atpase motor of the sec translocase. upon encounter, the signal peptide forms an alpha-helix that inserts into a flexible and elongated groove in seca. the mode of binding is bimodal, with both hydrophobic and electrostatic interac ...	2007	18022369
the process of mrna-trna translocation.	in the elongation cycle of translation, translocation is the process that advances the mrna-trna moiety on the ribosome, to allow the next codon to move into the decoding center. new results obtained by cryoelectron microscopy, interpreted in the light of x-ray structures and kinetic data, allow us to develop a model of the molecular events during translocation.	2007	18003906
proline modulates the intracellular redox environment and protects mammalian cells against oxidative stress.	the potential of proline to suppress reactive oxygen species (ros) and apoptosis in mammalian cells was tested by manipulating intracellular proline levels exogenously and endogenously by overexpression of proline metabolic enzymes. proline was observed to protect cells against h(2)o(2), tert-butyl hydroperoxide, and a carcinogenic oxidative stress inducer but was not effective against superoxide generators such as menadione. oxidative stress protection by proline requires the secondary amine of ...	2007	18036351
proline modulates the intracellular redox environment and protects mammalian cells against oxidative stress.	the potential of proline to suppress reactive oxygen species (ros) and apoptosis in mammalian cells was tested by manipulating intracellular proline levels exogenously and endogenously by overexpression of proline metabolic enzymes. proline was observed to protect cells against h(2)o(2), tert-butyl hydroperoxide, and a carcinogenic oxidative stress inducer but was not effective against superoxide generators such as menadione. oxidative stress protection by proline requires the secondary amine of ...	2007	18036351
knotted and topologically complex proteins as models for studying folding and stability.	among proteins of known three-dimensional structure, only a few possess complex topological features such as knotted or interlinked (catenated) protein backbones. such unusual proteins offer potentially unique insights into folding pathways and stabilization mechanisms. they also present special challenges for both theorists and computational scientists interested in understanding and predicting protein-folding behavior. here, we review complex topological features in proteins with a focus on re ...	2007	17967433
rna catalysis: ribozymes, ribosomes, and riboswitches.	the catalytic mechanisms employed by rna are chemically more diverse than initially suspected. divalent metal ions, nucleobases, ribosyl hydroxyl groups, and even functional groups on metabolic cofactors all contribute to the various strategies employed by rna enzymes. this catalytic breadth raises intriguing evolutionary questions about how rna lost its biological role in some cases, but not in others, and what catalytic roles rna might still be playing in biology.	2007	17981494
detecting coevolution in and among protein domains.	correlated changes of nucleic or amino acids have provided strong information about the structures and interactions of molecules. despite the rich literature in coevolutionary sequence analysis, previous methods often have to trade off between generality, simplicity, phylogenetic information, and specific knowledge about interactions. furthermore, despite the evidence of coevolution in selected protein families, a comprehensive screening of coevolution among all protein domains is still lacking. ...	2007	17983264
development of a novel one-tube isothermal reverse transcription thermophilic helicase-dependent amplification platform for rapid rna detection.	the high complexity and cost of polymerase chain reaction-based molecular diagnostics sometimes limits their use in the clinical diagnostics setting. a new helicase-based isothermal amplification method offers an alternative to standard polymerase chain reaction, allowing amplification and detection of specific dna sequences at a constant reaction temperature without thermocycling equipment. herein, we describe the development of a novel one-tube isothermal reverse transcription-thermophilic hel ...	2007	17975029
phenylalanyl-trna synthetase editing defects result in efficient mistranslation of phenylalanine codons as tyrosine.	translational quality control is monitored at several steps, including substrate selection by aminoacyl-trna synthetases (aarss), and discrimination of aminoacyl-trnas by elongation factor tu (ef-tu) and the ribosome. phenylalanyl-trna synthetase (phers) misactivates tyr but is able to correct the mistake using a proofreading activity named editing. previously we found that overproduction of editing-defective phers resulted in tyr incorporation at phe-encoded positions in vivo, although the misr ...	2007	17804641
first experimental evidence for the preferential stabilization of the natural d- over the nonnatural l-configuration in nucleic acids.	the homochirality of biomolecules is a prerequisite for the origin and evolution of terrestrial life. the unique selection of d-monosaccharides, in particular, d-ribose in rna and d-deoxyribose in dna, leads to the construction of proteins by l-amino acids. this points to the exclusive role of stereoselectivity in the most important physiological processes. so far, there is no experimental confirmation for the theoretical calculations of the energy differences between enantiomers used for the ex ...	2007	17804644
specific interaction between ef-g and rrf and its implication for gtp-dependent ribosome splitting into subunits.	after termination of protein synthesis, the bacterial ribosome is split into its 30s and 50s subunits by the action of ribosome recycling factor (rrf) and elongation factor g (ef-g) in a guanosine 5'-triphosphate (gtp)-hydrolysis-dependent manner. based on a previous cryo-electron microscopy study of ribosomal complexes, we have proposed that the binding of ef-g to an rrf-containing posttermination ribosome triggers an interdomain rotation of rrf, which destabilizes two strong intersubunit bridg ...	2007	17996252
transfer rna in the hybrid p/e state: correlating molecular dynamics simulations with cryo-em data.	transfer rna (trna) transiently occupies the hybrid p/e state (p/e-trna) when mrna-trna are translocated in the ribosome. in this study, we characterize the structure of p/e-trna and its interactions with the ribosome by correlating the results from molecular dynamics simulations on free trna with the cryo-em map of p/e-trna. in our approach, we show that the cryo-em map may be interpreted as a conformational average. along the molecular dynamics trajectories (44 ns, 18 ns, and 18 ns), some of t ...	2007	17925437
an expanded set of amino acid analogs for the ribosomal translation of unnatural peptides.	the application of in vitro translation to the synthesis of unnatural peptides may allow the production of extremely large libraries of highly modified peptides, which are a potential source of lead compounds in the search for new pharmaceutical agents. the specificity of the translation apparatus, however, limits the diversity of unnatural amino acids that can be incorporated into peptides by ribosomal translation. we have previously shown that over 90 unnatural amino acids can be enzymatically ...	2007	17912351
virus-encoded aminoacyl-trna synthetases: structural and functional characterization of mimivirus tyrrs and metrs.	aminoacyl-trna synthetases are pivotal in determining how the genetic code is translated in amino acids and in providing the substrate for protein synthesis. as such, they fulfill a key role in a process universally conserved in all cellular organisms from their most complex to their most reduced parasitic forms. in contrast, even complex viruses were not found to encode much translation machinery, with the exception of isolated components such as trnas. in this context, the discovery of four am ...	2007	17855524
the activities and function of molecular chaperones in the endoplasmic reticulum.	most proteins in the secretory pathway are translated, folded, and subjected to quality control at the endoplasmic reticulum (er). these processes must be flexible enough to process diverse protein conformations, yet specific enough to recognize when a protein should be degraded. molecular chaperones are responsible for this decision making process. er associated chaperones assist in polypeptide translocation, protein folding, and er associated degradation (erad). nevertheless, we are only begin ...	2007	17964199
molecular architecture of strictosidine glucosidase: the gateway to the biosynthesis of the monoterpenoid indole alkaloid family.	strictosidine beta-d-glucosidase (sg) follows strictosidine synthase (str1) in the production of the reactive intermediate required for the formation of the large family of monoterpenoid indole alkaloids in plants. this family is composed of approximately 2000 structurally diverse compounds. sg plays an important role in the plant cell by activating the glucoside strictosidine and allowing it to enter the multiple indole alkaloid pathways. here, we report detailed three-dimensional information d ...	2007	17890378
mg2+ binding and archaeosine modification stabilize the g15 c48 levitt base pair in trnas.	the g15-c48 levitt base pair, located at a crucial position in the core of canonical trnas, assumes a reverse watson-crick (rwc) geometry. by means of bioinformatics analysis and quantum mechanics calculations we show here that such a geometry is moderately more stable than an alternative bifurcated trans geometry, involving the guanine watson-crick face and the cytosine keto group, which we have also found in known rna structures. however we also demonstrate that the rwc geometry can take advan ...	2007	17652139
the primordial metabolism: an ancestral interconnection between leucine, arginine, and lysine biosynthesis.	it is generally assumed that primordial cells had small genomes with simple genes coding for enzymes able to react with a wide range of chemically related substrates, interconnecting different metabolic routes. new genes coding for enzymes with a narrowed substrate specificity arose by paralogous duplication(s) of ancestral ones and evolutionary divergence. in this way new metabolic pathways were built up by primordial cells. useful hints to disclose the origin and evolution of ancestral metabol ...	2007	17767731
fr3d: finding local and composite recurrent structural motifs in rna 3d structures.	new methods are described for finding recurrent three-dimensional (3d) motifs in rna atomic-resolution structures. recurrent rna 3d motifs are sets of rna nucleotides with similar spatial arrangements. they can be local or composite. local motifs comprise nucleotides that occur in the same hairpin or internal loop. composite motifs comprise nucleotides belonging to three or more different rna strand segments or molecules. we use a base-centered approach to construct efficient, yet exhaustive sea ...	2007	17694311
fr3d: finding local and composite recurrent structural motifs in rna 3d structures.	new methods are described for finding recurrent three-dimensional (3d) motifs in rna atomic-resolution structures. recurrent rna 3d motifs are sets of rna nucleotides with similar spatial arrangements. they can be local or composite. local motifs comprise nucleotides that occur in the same hairpin or internal loop. composite motifs comprise nucleotides belonging to three or more different rna strand segments or molecules. we use a base-centered approach to construct efficient, yet exhaustive sea ...	2007	17694311
a quantitative kinetic scheme for 70 s translation initiation complex formation.	association of the 30 s initiation complex (30sic) and the 50 s ribosomal subunit, leading to formation of the 70 s initiation complex (70sic), is a critical step of the translation initiation pathway. the 70sic contains initiator trna, fmet-trna(fmet), bound in the p (peptidyl)-site in response to the aug start codon. we have formulated a quantitative kinetic scheme for the formation of an active 70sic from 30sic and 50 s subunits on the basis of parallel rapid kinetics measurements of gtp hydr ...	2007	17868692
classification and regression tree (cart) analyses of genomic signatures reveal sets of tetramers that discriminate temperature optima of archaea and bacteria.	classification and regression tree (cart) analysis was applied to genome-wide tetranucleotide frequencies (genomic signatures) of 195 archaea and bacteria. although genomic signatures have typically been used to classify evolutionary divergence, in this study, convergent evolution was the focus. temperature optima for most of the organisms examined could be distinguished by cart analyses of tetranucleotide frequencies. this suggests that pervasive (nonlinear) qualities of genomes may reflect cer ...	2007	19054742
classification and regression tree (cart) analyses of genomic signatures reveal sets of tetramers that discriminate temperature optima of archaea and bacteria.	classification and regression tree (cart) analysis was applied to genome-wide tetranucleotide frequencies (genomic signatures) of 195 archaea and bacteria. although genomic signatures have typically been used to classify evolutionary divergence, in this study, convergent evolution was the focus. temperature optima for most of the organisms examined could be distinguished by cart analyses of tetranucleotide frequencies. this suggests that pervasive (nonlinear) qualities of genomes may reflect cer ...	2007	19054742
crystal structure of hyperthermophilic esterase este1 and the relationship between its dimerization and thermostability properties.	este1 is a hyperthermophilic esterase belonging to the hormone-sensitive lipase family and was originally isolated by functional screening of a metagenomic library constructed from a thermal environmental sample. dimers and oligomers may have been evolutionally selected in thermophiles because intersubunit interactions can confer thermostability on the proteins. the molecular mechanisms of thermostabilization of this extremely thermostable esterase are not well understood due to the lack of stru ...	2007	17625021
a computational pipeline for high- throughput discovery of cis-regulatory noncoding rna in prokaryotes.	noncoding rnas (ncrnas) are important functional rnas that do not code for proteins. we present a highly efficient computational pipeline for discovering cis-regulatory ncrna motifs de novo. the pipeline differs from previous methods in that it is structure-oriented, does not require a multiple-sequence alignment as input, and is capable of detecting rna motifs with low sequence conservation. we also integrate rna motif prediction with rna homolog search, which improves the quality of the rna mo ...	2007	17616982
nanoscale dewetting transition in protein complex folding.	in a previous study, a surprising drying transition was observed to take place inside the nanoscale hydrophobic channel in the tetramer of the protein melittin. the goal of this paper is to determine if there are other protein complexes capable of displaying a dewetting transition during their final stage of folding. we searched the entire protein data bank (pdb) for all possible candidates, including protein tetramers, dimers, and two-domain proteins, and then performed the molecular dynamics ( ...	2007	17608515
predicting helical coaxial stacking in rna multibranch loops.	the hypothesis that rna coaxial stacking can be predicted by free energy minimization using nearest-neighbor parameters is tested. the results show 58.2% positive predictive value (ppv) and 65.7% sensitivity for accuracy of the lowest free energy configuration compared with crystal structures. the probability of each stacking configuration can be predicted using a partition function calculation. based on the dependence of accuracy on the calculated probability of the stacks, a probability thresh ...	2007	17507661
advancements in the pathophysiology of friedreich's ataxia and new prospects for treatments.	on november 9-12, 2006, the friedreich's ataxia research alliance (fara) and the national institutes of health (nih) hosted the third international friedreich's ataxia (frda) scientific conference at the nih in bethesda, maryland, highlighting the exciting research leading now to a variety of clinical trials that show promise of effective treatments for this devastating disorder. nearly 150 leading frda scientists from around the world discussed their new insights and findings. the presence of s ...	2007	17596984
type-2 isopentenyl diphosphate isomerase. mechanistic studies with cyclopropyl and epoxy analogues.		2007	17547410
viral proteomics.	viruses have long been studied not only for their pathology and associated disease but also as model systems for molecular processes and as tools for identifying important cellular regulatory proteins and pathways. recent advances in mass spectrometry methods coupled with the development of proteomic approaches have greatly facilitated the detection of virion components, protein interactions in infected cells, and virally induced changes in the cellular proteome, resulting in a more comprehensiv ...	2007	17554050
mechanism for expanding the decoding capacity of transfer rnas by modification of uridines.	one of the most prevalent base modifications involved in decoding is uridine 5-oxyacetic acid at the wobble position of trna. it has been known for several decades that this modification enables a single trna to decode all four codons in a degenerate codon box. we have determined structures of an anticodon stem-loop of trna(val) containing the modified uridine with all four valine codons in the decoding site of the 30s ribosomal subunit. an intramolecular hydrogen bond involving the modification ...	2007	17496902
single molecule transcription profiling with afm.	established techniques for global gene expression profiling, such as microarrays, face fundamental sensitivity constraints. due to greatly increasing interest in examining minute samples from micro-dissected tissues, including single cells, unorthodox approaches, including molecular nanotechnologies, are being explored in this application. here, we examine the use of single molecule, ordered restriction mapping, combined with afm, to measure gene transcription levels from very low abundance samp ...	2007	20721301
posttranslational synthesis of hypusine: evolutionary progression and specificity of the hypusine modification.	a naturally occurring unusual amino acid, hypusine [n (epsilon)-(4-amino-2-hydroxybutyl)-lysine] is a component of a single cellular protein, eukaryotic translation initiation factor 5a (eif5a). it is a modified lysine with structural contribution from the polyamine spermidine. hypusine is formed in a novel posttranslational modification that involves two enzymes, deoxyhypusine synthase (dhs) and deoxyhypusine hydroxylase (dohh). eif5a and deoxyhypusine/hypusine modification are essential for gr ...	2007	17476569
sympatric drosophila simulans flies with distinct mtdna show age related differences in mitochondrial metabolism.	the primary causes of age-related changes in mitochondrial metabolism are not known. the goal of this study is to document the influence of naturally occurring mtdna variation on age dependent changes in mitochondrial respiration, hydrogen peroxide (h(2)o(2)) generation and antioxidant defenses in the fly drosophila simulans. possible changes include an increase in rates of reactive oxygen species production with age and/or an age dependent decrease in antioxidant response. for this study we hav ...	2007	17681231
structural genomics and drug discovery.	structure determination has already proven useful for lead optimization and direct drug design. the number of high-resolution structures available in public databases today exceeds 30,000 and will definitely aid in structure-based drug design. structural genomics approaches covering whole genomes, topologically similar proteins or gene families are great assets for further progress in the development of new drugs. however, membrane proteins representing 70% of current drug targets are poorly cha ...	2007	17488474
loop anchor modification causes the population of an alternative native state in an sh3-like domain.	many stably folded proteins are proposed to contain long, unstructured loops. a series of hybrid proteins (ebe1-4) containing the folded scaffold of photosystem i accessory protein e (psae), an sh3-like protein, and the 40-residue heme-binding loop of cytochrome b(5) was created to inspect the dependence of thermodynamic and kinetic parameters on the residues at the interface of folded and flexible regions. compared to the simplest hybrid (ebe1), the chimeras differed by gly insertions (ebe2, eb ...	2007	17456740
anticodon-dependent conservation of bacterial trna gene sequences.	the residues in trna that account for its tertiary fold and for its specific aminoacylation are well understood. in contrast, relatively little is known about the residues in trna that dictate its ability to transit the different sites of the ribosome. yet protein synthesis cannot occur unless trna properly engages with the ribosome. this study analyzes trna gene sequences from 145 fully sequenced bacterial genomes. grouping the sequences according to the anticodon triplet reveals that many resi ...	2007	17379816
evolutionary rates vary among rrna structural elements.	understanding patterns of rrna evolution is critical for a number of fields, including structure prediction and phylogeny. the standard model of rna evolution is that compensatory mutations in stems make up the bulk of the changes between homologous sequences, while unpaired regions are relatively homogeneous. we show that considerable heterogeneity exists in the relative rates of evolution of different secondary structure categories (stems, loops, bulges, etc.) within the rrna, and that in euka ...	2007	17468501
rnammer: consistent and rapid annotation of ribosomal rna genes.	the publication of a complete genome sequence is usually accompanied by annotations of its genes. in contrast to protein coding genes, genes for ribosomal rna (rrna) are often poorly or inconsistently annotated. this makes comparative studies based on rrna genes difficult. we have therefore created computational predictors for the major rrna species from all kingdoms of life and compiled them into a program called rnammer. the program uses hidden markov models trained on data from the 5s ribosom ...	2007	17452365
biosynthesis of pantothenic acid and coenzyme a.	pantothenate is vitamin b5 and is the key precursor for the biosynthesis of coenzyme a (coa), a universal and essential cofactor involved in a myriad of metabolic reactions, including the synthesis of phospholipids, the synthesis and degradation of fatty acids, and the operation of the tricarboxylic acid cycle. coa is also the only source of the phosphopantetheine prosthetic group for enzymes that shuttle intermediates between the active sites of enzymes involved in fatty acid, nonribosomal pept ...	2007	26443589