Sujet(s)
Agrément de dispositif , Cardiopathies congénitales/thérapie , Prothèses et implants , Food and Drug Administration (USA) , Comités consultatifs , Enfant , Besoins et demandes de services de santé , Humains , Utilisation hors indication , Sécurité des patients , Évaluation de la technologie biomédicale , États-UnisRÉSUMÉ
The first structural representative of the domain of unknown function DUF2006 family, also known as Pfam family PF09410, comprises a lipocalin-like fold with domain duplication. The finding of the calycin signature in the N-terminal domain, combined with remote sequence similarity to two other protein families (PF07143 and PF08622) implicated in isoprenoid metabolism and the oxidative stress response, support an involvement in lipid metabolism. Clusters of conserved residues that interact with ligand mimetics suggest that the binding and regulation sites map to the N-terminal domain and to the interdomain interface, respectively.
Sujet(s)
Protéines bactériennes/composition chimique , Bases de données génétiques , Métabolisme lipidique , Nitrosomonas europaea/composition chimique , Séquence d'acides aminés , Cristallographie aux rayons X , Modèles moléculaires , Données de séquences moléculaires , Nitrosomonas europaea/métabolisme , Stress oxydatif , Structure tertiaire des protéines , Alignement de séquences , Similitude de séquences d'acides aminésRÉSUMÉ
Proteins with the DUF2063 domain constitute a new Pfam family, PF09836. The crystal structure of a member of this family, NGO1945 from Neisseria gonorrhoeae, has been determined and reveals that the N-terminal DUF2063 domain is likely to be a DNA-binding domain. In conjunction with the rest of the protein, NGO1945 is likely to be involved in transcriptional regulation, which is consistent with genomic neighborhood analysis. Of the 216 currently known proteins that contain a DUF2063 domain, the most significant sequence homologs of NGO1945 (â¼40-99% sequence identity) are from various Neisseria and Haemophilus species. As these are important human pathogens, NGO1945 represents an interesting candidate for further exploration via biochemical studies and possible therapeutic intervention.
Sujet(s)
Protéines bactériennes/composition chimique , Régulation de l'expression des gènes , Neisseria gonorrhoeae/composition chimique , Transcription génétique , Séquence d'acides aminés , Protéines bactériennes/génétique , Cristallographie aux rayons X , Génome bactérien , Modèles moléculaires , Données de séquences moléculaires , Neisseria gonorrhoeae/génétique , Structure quaternaire des protéines , Structure tertiaire des protéines , Similitude structurale de protéinesRÉSUMÉ
The crystal structures of BB2672 and SPO0826 were determined to resolutions of 1.7 and 2.1â Å by single-wavelength anomalous dispersion and multiple-wavelength anomalous dispersion, respectively, using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). These proteins are the first structural representatives of the PF06684 (DUF1185) Pfam family. Structural analysis revealed that both structures adopt a variant of the Bacillus chorismate mutase fold (BCM). The biological unit of both proteins is a hexamer and analysis of homologs indicates that the oligomer interface residues are highly conserved. The conformation of the critical regions for oligomerization appears to be dependent on pH or salt concentration, suggesting that this protein might be subject to environmental regulation. Structural similarities to BCM and genome-context analysis suggest a function in amino-acid synthesis.
Sujet(s)
Acides aminés/métabolisme , Bordetella bronchiseptica/enzymologie , Chorismate mutase/composition chimique , Pliage des protéines , Rhodobacteraceae/enzymologie , Séquence d'acides aminés , Bacillus/enzymologie , Chorismate mutase/métabolisme , Cristallographie aux rayons X , Modèles moléculaires , Données de séquences moléculaires , Structure quaternaire des protéines , Structure tertiaire des protéines , Similitude structurale de protéinesRÉSUMÉ
The crystal structure of Jann_2411 from Jannaschia sp. strain CCS1, a member of the Pfam PF07336 family classified as a domain of unknown function (DUF1470), was solved to a resolution of 1.45â Å by multiple-wavelength anomalous dispersion (MAD). This protein is the first structural representative of the DUF1470 Pfam family. Structural analysis revealed a two-domain organization, with the N-terminal domain presenting a new fold called the ABATE domain that may bind an as yet unknown ligand. The C-terminal domain forms a treble-clef zinc finger that is likely to be involved in DNA binding. Analysis of the Jann_2411 protein and the broader ABATE-domain family suggests a role as stress-induced transcriptional regulators.
Sujet(s)
Protéines bactériennes/composition chimique , Rhodobacteraceae/composition chimique , Séquence d'acides aminés , Cristallographie aux rayons X , Modèles moléculaires , Données de séquences moléculaires , Structure quaternaire des protéines , Structure tertiaire des protéines , Alignement de séquences , Doigts de zincRÉSUMÉ
The structure of LP2179, a member of the PF08866 (DUF1831) family, suggests a novel α+ß fold comprising two ß-sheets packed against a single helix. A remote structural similarity to two other uncharacterized protein families specific to the Bacillus genus (PF08868 and PF08968), as well as to prokaryotic S-adenosylmethionine decarboxylases, is consistent with a role in amino-acid metabolism. Genomic neighborhood analysis of LP2179 supports this functional assignment, which might also then be extended to PF08868 and PF08968.
Sujet(s)
Acides aminés/métabolisme , Protéines bactériennes/composition chimique , Lactobacillus plantarum/composition chimique , Pliage des protéines , Séquence d'acides aminés , Protéines bactériennes/métabolisme , Cristallographie aux rayons X , Lactobacillus plantarum/métabolisme , Modèles moléculaires , Données de séquences moléculaires , Structure tertiaire des protéines , Alignement de séquences , Similitude structurale de protéinesRÉSUMÉ
The crystal structure of PA1994 from Pseudomonas aeruginosa, a member of the Pfam PF06475 family classified as a domain of unknown function (DUF1089), reveals a novel fold comprising a 15-stranded ß-sheet wrapped around a single α-helix that assembles into a tight dimeric arrangement. The remote structural similarity to lipoprotein localization factors, in addition to the presence of an acidic pocket that is conserved in DUF1089 homologs, phospholipid-binding and sugar-binding proteins, indicate a role for PA1994 and the DUF1089 family in glycolipid metabolism. Genome-context analysis lends further support to the involvement of this family of proteins in glycolipid metabolism and indicates possible activation of DUF1089 homologs under conditions of bacterial cell-wall stress or host-pathogen interactions.
Sujet(s)
Protéines bactériennes/composition chimique , Glycolipides/métabolisme , Pliage des protéines , Pseudomonas aeruginosa/composition chimique , Séquence d'acides aminés , Protéines bactériennes/génétique , Protéines bactériennes/métabolisme , Cristallographie aux rayons X , Génome bactérien , Modèles moléculaires , Données de séquences moléculaires , Structure quaternaire des protéines , Structure tertiaire des protéines , Pseudomonas aeruginosa/génétique , Pseudomonas aeruginosa/métabolismeRÉSUMÉ
YeaZ is involved in a protein network that is essential for bacteria. The crystal structure of YeaZ from Thermotoga maritima was determined to 2.5â Å resolution. Although this protein belongs to a family of ancient actin-like ATPases, it appears that it has lost the ability to bind ATP since it lacks some key structural features that are important for interaction with ATP. A conserved surface was identified, supporting its role in the formation of protein complexes.
Sujet(s)
Protéines bactériennes/composition chimique , Thermotoga maritima/composition chimique , Séquence d'acides aminés , Cristallographie aux rayons X , Modèles moléculaires , Données de séquences moléculaires , Structure quaternaire des protéines , Structure tertiaire des protéines , Alignement de séquencesRÉSUMÉ
KPN03535 (gi|152972051) is a putative lipoprotein of unknown function that is secreted by Klebsiella pneumoniae MGH 78578. The crystal structure reveals that despite a lack of any detectable sequence similarity to known structures, it is a novel variant of the OB-fold and structurally similar to the bacterial Cpx-pathway protein NlpE, single-stranded DNA-binding (SSB) proteins and toxins. K. pneumoniae MGH 78578 forms part of the normal human skin, mouth and gut flora and is an opportunistic pathogen that is linked to about 8% of all hospital-acquired infections in the USA. This structure provides the foundation for further investigations into this divergent member of the OB-fold family.
Sujet(s)
Protéines bactériennes/composition chimique , Klebsiella pneumoniae/composition chimique , Lipoprotéines/composition chimique , Séquence d'acides aminés , Cristallographie aux rayons X , Modèles moléculaires , Données de séquences moléculaires , Pliage des protéines , Structure tertiaire des protéinesRÉSUMÉ
A novel aminoacyl-tRNA synthetase that contains an iron-sulfur cluster in the tRNA anticodon-binding region and efficiently charges tRNA with tryptophan has been found in Thermotoga maritima. The crystal structure of TmTrpRS (tryptophanyl-tRNA synthetase; TrpRS; EC 6.1.1.2) reveals an iron-sulfur [4Fe-4S] cluster bound to the tRNA anticodon-binding (TAB) domain and an L-tryptophan ligand in the active site. None of the other T. maritima aminoacyl-tRNA synthetases (AARSs) contain this [4Fe-4S] cluster-binding motif (C-x22-C-x6-C-x2-C). It is speculated that the iron-sulfur cluster contributes to the stability of TmTrpRS and could play a role in the recognition of the anticodon.
Sujet(s)
Ferrosulfoprotéines/composition chimique , Thermotoga maritima/enzymologie , Tryptophane-tRNA ligase/composition chimique , Séquence d'acides aminés , Animaux , Séquence conservée , Cristallographie aux rayons X , Humains , Ligands , Modèles moléculaires , Données de séquences moléculaires , Structure quaternaire des protéines , Structure tertiaire des protéines , Alignement de séquencesRÉSUMÉ
In the plant pathogen Xanthomonas campestris pv. campestris, the product of the tcmJ gene, XcTcmJ, encodes a protein belonging to the RmlC family of cupins. XcTcmJ was crystallized in a monoclinic space group (C2) in the presence of zinc acetate and the structure was determined to 1.6â Å resolution. Previously, the apo structure has been reported in the absence of any bound metal ion [Chin et al. (2006), Proteins, 65, 1046-1050]. The most significant difference between the apo structure and the structure of XcTcmJ described here is a reorganization of the binding site for zinc acetate, which was most likely acquired from the crystallization solution. This site is located in the conserved metal ion-binding domain at the putative active site of XcTcmJ. In addition, an acetate was also bound within coordination distance of the zinc. In order to accommodate this binding, rearrangement of a conserved histidine ligand is required as well as several nearby residues within and around the putative active site. These observations indicate that binding of zinc serves a functional role in this cupin protein.
Sujet(s)
Protéines bactériennes/composition chimique , Domaine catalytique , Xanthomonas campestris/composition chimique , Acétate de zinc/composition chimique , Séquence d'acides aminés , Protéines bactériennes/métabolisme , Séquence conservée , Cristallographie aux rayons X , Modèles moléculaires , Données de séquences moléculaires , Motifs et domaines d'intéraction protéique , Alignement de séquences , Similitude structurale de protéines , Xanthomonas campestris/métabolisme , Acétate de zinc/métabolismeRÉSUMÉ
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 (TmMre11) and the first such structure from eubacteria. TmMre11 and PfMre11 display similar overall structures, despite sequence identity in the twilight zone of only approximately 20%. However, they differ substantially in their DNA-specificity domains and in their dimeric organization. Residues in the nuclease domain are highly conserved, but those in the DNA-specificity domain are not. The structural differences likely affect how Mre11 from different organisms recognize and interact with single-stranded DNA, double-stranded DNA and DNA hairpin structures during DNA repair. The TmMre11 nuclease active site has no bound metal ions, but is conserved in sequence and structure with the exception of a histidine that is important in PfMre11 nuclease activity. Nevertheless, biochemical characterization confirms that TmMre11 possesses both endonuclease and exonuclease activities on single-stranded and double-stranded DNA substrates, respectively.
Sujet(s)
Protéines bactériennes/composition chimique , Réparation de l'ADN , ADN simple brin/composition chimique , ADN/composition chimique , Endodeoxyribonucleases/composition chimique , Exodeoxyribonucleases/composition chimique , Thermotoga maritima/enzymologie , Séquence d'acides aminés , Cristallographie aux rayons X , ADN/génétique , ADN simple brin/génétique , Endodeoxyribonucleases/génétique , Exodeoxyribonucleases/génétique , Modèles chimiques , Données de séquences moléculaires , Conformation des protéines , Similitude de séquences d'acides aminésRÉSUMÉ
SsgA-like proteins (SALPs) are a family of homologous cell division-related proteins that occur exclusively in morphologically complex actinomycetes. We show that SsgB, a subfamily of SALPs, is the archetypal SALP that is functionally conserved in all sporulating actinomycetes. Sporulation-specific cell division of Streptomyces coelicolor ssgB mutants is restored by introduction of distant ssgB orthologues from other actinomycetes. Interestingly, the number of septa (and spores) of the complemented null mutants is dictated by the specific ssgB orthologue that is expressed. The crystal structure of the SsgB from Thermobifida fusca was determined at 2.6 A resolution and represents the first structure for this family. The structure revealed similarities to a class of eukaryotic "whirly" single-stranded DNA/RNA-binding proteins. However, the electro-negative surface of the SALPs suggests that neither SsgB nor any of the other SALPs are likely to interact with nucleotide substrates. Instead, we show that a conserved hydrophobic surface is likely to be important for SALP function and suggest that proteins are the likely binding partners.
Sujet(s)
Actinobacteria/métabolisme , Protéines bactériennes/composition chimique , Protéines bactériennes/physiologie , Séquence d'acides aminés , Sites de fixation , Division cellulaire , Cryomicroscopie électronique , Cristallographie aux rayons X/méthodes , Escherichia coli/métabolisme , Test de complémentation , Microscopie de fluorescence/méthodes , Microscopie de contraste de phase/méthodes , Données de séquences moléculaires , Mutation , Similitude de séquences d'acides aminés , Spores bactériensRÉSUMÉ
Cell-cycle-regulated stalk biogenesis in Caulobacter crescentus is controlled by a multistep phosphorelay system consisting of the hybrid histidine kinase ShkA, the histidine phosphotransfer (HPt) protein ShpA, and the response regulator TacA. ShpA shuttles phosphoryl groups between ShkA and TacA. When phosphorylated, TacA triggers a downstream transcription cascade for stalk synthesis in an RpoN-dependent manner. The crystal structure of ShpA was determined to 1.52 A resolution. ShpA belongs to a family of monomeric HPt proteins that feature a highly conserved four-helix bundle. The phosphorylatable histidine His56 is located on the surface of the helix bundle and is fully solvent exposed. One end of the four-helix bundle in ShpA is shorter compared with other characterized HPt proteins, whereas the face that potentially interacts with the response regulators is structurally conserved. Similarities of the interaction surface around the phosphorylation site suggest that ShpA is likely to share a common mechanism for molecular recognition and phosphotransfer with yeast phosphotransfer protein YPD1 despite their low overall sequence similarity.
Sujet(s)
Protéines bactériennes/composition chimique , Caulobacter crescentus/métabolisme , Histidine/métabolisme , Modèles moléculaires , Phosphotransferases/composition chimique , Séquence d'acides aminés , Protéines bactériennes/métabolisme , Cristallographie aux rayons X , Données de séquences moléculaires , Phosphorylation , Phosphotransferases/métabolisme , Conformation des protéinesRÉSUMÉ
The crystal structures of two homologous endopeptidases from cyanobacteria Anabaena variabilis and Nostoc punctiforme were determined at 1.05 and 1.60 A resolution, respectively, and contain a bacterial SH3-like domain (SH3b) and a ubiquitous cell-wall-associated NlpC/P60 (or CHAP) cysteine peptidase domain. The NlpC/P60 domain is a primitive, papain-like peptidase in the CA clan of cysteine peptidases with a Cys126/His176/His188 catalytic triad and a conserved catalytic core. We deduced from structure and sequence analysis, and then experimentally, that these two proteins act as gamma-D-glutamyl-L-diamino acid endopeptidases (EC 3.4.22.-). The active site is located near the interface between the SH3b and NlpC/P60 domains, where the SH3b domain may help define substrate specificity, instead of functioning as a targeting domain, so that only muropeptides with an N-terminal L-alanine can bind to the active site.
Sujet(s)
Endopeptidases/composition chimique , Endopeptidases/métabolisme , Peptidoglycane/composition chimique , Peptidoglycane/métabolisme , Séquence d'acides aminés , Anabaena variabilis/composition chimique , Anabaena variabilis/enzymologie , Domaine catalytique , Cysteine endopeptidases/composition chimique , Cysteine endopeptidases/métabolisme , Cysteine endopeptidases/physiologie , Endopeptidases/physiologie , Modèles biologiques , Modèles moléculaires , Données de séquences moléculaires , Nostoc/composition chimique , Nostoc/enzymologie , Fragments peptidiques/composition chimique , Fragments peptidiques/métabolisme , Structure tertiaire des protéines , Similitude de séquences d'acides aminés , Spécificité du substrat , Domaine d'homologie SRCRÉSUMÉ
ECX21941 represents a very large family (over 600 members) of novel, ocean metagenome-specific proteins identified by clustering of the dataset from the Global Ocean Sampling expedition. The crystal structure of ECX21941 reveals unexpected similarity to Sm/LSm proteins, which are important RNA-binding proteins, despite no detectable sequence similarity. The ECX21941 protein assembles as a homopentamer in solution and in the crystal structure when expressed in Escherichia coli and represents the first pentameric structure for this Sm/LSm family of proteins, although the actual oligomeric form in vivo is currently not known. The genomic neighborhood analysis of ECX21941 and its homologs combined with sequence similarity searches suggest a cyanophage origin for this protein. The specific functions of members of this family are unknown, but our structure analysis of ECX21941 indicates nucleic acid-binding capabilities and suggests a role in RNA and/or DNA processing.