Knowledge of toxins, virulence factors and antibiotic resistance genes is essential for bio-defense applications aimed at identifying 'functional' signatures for characterizing emerging or engineered ...pathogens. Whereas genetic signatures identify a pathogen, functional signatures identify what a pathogen is capable of. To facilitate rapid identification of sequences and characterization of genes for signature discovery, we have collected all publicly available (as of this writing), organized sequences representing known toxins, virulence factors, and antibiotic resistance genes in one convenient database, which we believe will be of use to the bio-defense research community. MvirDB integrates DNA and protein sequence information from Tox-Prot, SCORPION, the PRINTS virulence factors, VFDB, TVFac, Islander, ARGO and a subset of VIDA. Entries in MvirDB are hyperlinked back to their original sources. A blast tool allows the user to blast against all DNA or protein sequences in MvirDB, and a browser tool allows the user to search the database to retrieve virulence factor descriptions, sequences, and classifications, and to download sequences of interest. MvirDB has an automated weekly update mechanism. Each protein sequence in MvirDB is annotated using our fully automated protein annotation system and is linked to that system's browser tool. MvirDB can be accessed at http://mvirdb.llnl.gov/.
Knowledge of toxins, virulence factors and antibiotic resistance genes is essential for bio-defense applications aimed at identifying 'functional' signatures for characterizing emerging or engineered ...pathogens. Whereas genetic signatures identify a pathogen, functional signatures identify what a pathogen is capable of. To facilitate rapid identification of sequences and characterization of genes for signature discovery, we have collected all publicly available (as of this writing), organized sequences representing known toxins, virulence factors, and antibiotic resistance genes in one convenient database, which we believe will be of use to the bio-defense research community. MvirDB integrates DNA and protein sequence information from Tox-Prot, SCORPION, the PRINTS virulence factors, VFDB, TVFac, Islander, ARGO and a subset of VIDA. Entries in MvirDB are hyperlinked back to their original sources. A blast tool allows the user to blast against all DNA or protein sequences in MvirDB, and a browser tool allows the user to search the database to retrieve virulence factor descriptions, sequences, and classifications, and to download sequences of interest. MvirDB has an automated weekly update mechanism. Each protein sequence in MvirDB is annotated using our fully automated protein annotation system and is linked to that system's browser tool. MvirDB can be accessed at http://mvirdb.llnl.gov/.
RNA-dependent RNA polymerase (RdRp) is essential to viral replication and is therefore one of the primary targets of countermeasures against these dangerous infectious agents. Development of ...broad-spectrum therapeutics targeting polymerases has been hampered by the extreme sequence variability of these sequences. RdRps range in length from 400-800 residues, yet contain only ∼20 residues that are conserved in most species. In this study, we made structure-based comparisons that are independent of sequence composition using a recently developed algorithm. We identified residue-to-residue correspondences of multiple protein structures and created (two-dimensional) structure-based alignment maps of 37 polymerase structures that provide both sequence and structure details. Using these maps, we determined that ∼75% of each polymerase species consists of seven protein segments, each of which has high structural similarity to segments in other species, though they are widely divergent in sequence composition and order. We define each of these segments as a 'homomorph', and each includes (though most are much larger than) the well-known conserved polymerase motifs. All homomorphs contact the template tunnel or nucleoside triphosphate (NTP) entry tunnel and the exterior of the protein, suggesting they constitute a structural and functional skeleton common among the polymerases.
Mortality rate from bladder cancer in Europe is the highest in its Central Region. This study is an attempt to find underlying factors by proper characterisation of large cohort of Polish patients ...with bladder cancer.This is a multicentre study enrolling 1360 consecutive patients diagnosed with primary urothelial carcinoma of the bladder in years 2012-2013 in Poland. All patients underwent transurethral resection of the bladder tumor. Data on staging and grading of all cancers were collected, as well as several demographic and clinical factors were tested for the association with muscle invasiveness of the cancer.Mean age of the cohort was 69.6 years, male to female ratio was 3:1. Bladder cancer stage Ta, T1 and muscle-invasive (MIBC) was diagnosed in 533 (39.2%), 516 (37.9%) and 296 (21.8%) patients, respectively. Patients with MIBC were older (73 vs. 68 years, p<0.05), had lower body mass index (25.4 vs. 26.5 kg/m2, p<0.05), lower haemoglobin concentration (12.2 vs. 13.4 mg/l, p<0.05), longer history of haematuria (86.2 vs. 74.4 days) and longer time interval from first symptom to diagnosis (118.0 vs. 88.2 days), compared to patients with Ta and T1 tumors.High mortality rate from bladder cancer in Central Europe can result from very high incidence of high-risk T1 tumors and high prevalence of prognostic factors of poor survival.
We present a set of programs and a website designed to facilitate protein structure comparison and protein structure modeling efforts. Our protein structure analysis and comparison services use the ...LGA (local-global alignment) program to search for regions of local similarity and to evaluate the level of structural similarity between compared protein structures. To facilitate the homology-based protein structure modeling process, our AL2TS service translates given sequence–structure alignment data into the standard Protein Data Bank (PDB) atom records (coordinates). For a given sequence of amino acids, the AS2TS (amino acid sequence to tertiary structure) system calculates (e.g. using PSI-BLAST PDB analysis) a list of the closest proteins from the PDB, and then a set of draft 3D models is automatically created. Web services are available at http://as2ts.llnl.gov/.
We have examined the elbow angles for 365 different Fab fragments, and observe that Fabs with λ light chains have adopted a wider range of elbow angles than their κ chain counterparts, and that the λ ...light chain Fabs are frequently found with very large (>195°) elbow angles. This apparent hyperflexibility of λ chain Fabs may be due to an insertion in their switch region, which is one residue longer than in κ chains, with glycine occurring most frequently at the insertion position. A new, web-based computer program that was used to calculate the Fab elbow angles is described.
Bovine enteroviruses are members of the family Picornaviridae, genus Enterovirus. Whilst little is known about their pathogenic potential, they are apparently endemic in some cattle and cattle ...environments. Only one of the two current serotypes has been sequenced completely. In this report, the entire genome sequences of bovine enterovirus 2 (BEV-2) strain PS87 and a recent isolate from an endemically infected herd in Maryland, USA (Wye3A) are presented. The recent isolate clearly segregated phylogenetically with sequences representing the BEV-2 serotype, as did other isolates from the endemic herd. The Wye3A isolate shared 82 % nucleotide sequence identity with the PS87 strain and 68 % identity with a BEV-1 strain (VG5-27). Comparison of BEV-2 and BEV-1 deduced protein sequences revealed 72-73 % identity and showed that most differences were single amino acid changes or single deletions, with the exception of the VP1 protein, where both BEV-2 sequences were 7 aa shorter than that of BEV-1. Homology modelling of the capsid proteins of BEV-2 against protein database entries for picornaviruses indicated six significant differences among bovine enteroviruses and other members of the family Picornaviridae. Five of these were on the 'rim' of the proposed enterovirus receptor-binding site or 'canyon' (VP1) and one was near the base of the canyon (VP3). Two of these regions varied enough to distinguish BEV-2 from BEV-1 strains. This is the first report and analysis of full-length sequences for BEV-2. Continued analysis of these wild-type strains should yield useful information for genotyping enteroviruses and modelling enterovirus capsid structure.
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