Blast sampling for structural and functional analyses

BACKGROUND: The post-genomic era is characterised by a torrent of biological information flooding the public databases. As a direct consequence, similarity searches starting with a single query sequence frequently lead to the identification of hundreds, or even thousands of potential homologues. The huge volume of data renders the subsequent structural, functional and evolutionary analyses very difficult. It is therefore essential to develop new strategies for efficient sampling of this large sequence space, in order to reduce the number of sequences to be processed. At the same time, it is important to retain the most pertinent sequences for structural and functional studies. RESULTS: An exhaustive analysis on a large scale test set (284 protein families) was performed to compare the efficiency of four different sampling methods aimed at selecting the most pertinent sequences. These four methods sample the proteins detected by BlastP searches and can be divided into two categories: two customisable methods where the user defines either the maximal number or the percentage of sequences to be selected; two automatic methods in which the number of sequences selected is determined by the program. We focused our analysis on the potential information content of the sampled sets of sequences using multiple alignment of complete sequences as the main validation tool. The study considered two criteria: the total number of sequences in BlastP and their associated E-values. The subsequent analyses investigated the influence of the sampling methods on the E-value distributions, the sequence coverage, the final multiple alignment quality and the active site characterisation at various residue conservation thresholds as a function of these criteria. CONCLUSION: The comparative analysis of the four sampling methods allows us to propose a suitable sampling strategy that significantly reduces the number of homologous sequences required for alignment, while at the same time maintaining the relevant information concerning the active site residues

euHCVdb: the European hepatitis C virus database

The hepatitis C virus (HCV) genome shows remarkable sequence variability, leading to the classification of at least six major genotypes, numerous subtypes and a myriad of quasispecies within a given host. A database allowing researchers to investigate the genetic and structural variability of all available HCV sequences is an essential tool for studies on the molecular virology and pathogenesis of hepatitis C as well as drug design and vaccine development. We describe here the European Hepatitis C Virus Database (euHCVdb, ), a collection of computer-annotated sequences based on reference genomes. The annotations include genome mapping of sequences, use of recommended nomenclature, subtyping as well as three-dimensional (3D) molecular models of proteins. A WWW interface has been developed to facilitate database searches and the export of data for sequence and structure analyses. As part of an international collaborative effort with the US and Japanese databases, the European HCV Database (euHCVdb) is mainly dedicated to HCV protein sequences, 3D structures and functional analyses

OLIGOSACCHARIDES ET XENOTRANSPLANTATION (ETUDE ET PRODUCTION PAR VOIE BIOTECHNOLOGIQUE DU XENOANTIGENE GALGAL MODELISATION DE L'3-GALACTOSYLTRANSFERASE)

GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

NRSAS: Nuclear Receptor Structure Analysis Servers

We present a coherent series of servers that can perform a large number of structure analyses on nuclear hormone receptors. These servers are part of the NucleaRDB project, which provides a powerful information system for nuclear hormone receptors. The computations performed by the servers include homology modelling, structure validation, calculating contacts, accessibility values, hydrogen bonding patterns, predicting mutations and a host of two- and three-dimensional visualisations. The Nuclear Receptor Structure Analysis Servers (NRSAS) are freely accessible at http://www.cmbi.kun.nl/NR/servers/html/ and in-house copies can be obtained upon request

NRMD: Nuclear Receptor Mutation Database

The NRMD is a database for nuclear receptor mutation information. It includes mutation information from SWISS-PROT/TrEMBL, several web-based mutation data resources, and data extracted from the literature in a fully automatic manner. Because it is also possible to add mutations manually, a hundred mutations were added for completeness. At present, the NRMD contains information about 893 mutations in 54 nuclear receptors. A common numbering scheme for all nuclear receptors eases the use of the information for many kinds of studies. The NRMD is freely available to academia and industry as a stand-alone version at: www.receptors.org/NR/

Casesidin-like anti-bacterial peptides in peptic hydrolysate of camel milk β-casein

The antibacterial activity of camel milk b-casein and its peptic hydrolysate was investigated. The hydrolysatewas fractionated by ultrafiltration successively through membranes with a 10 kDa and a 1 kDacut-off, sequentially. Antibacterial activity assays against Staphylococcus aureus CNRZ 3, Listeria innocuaATCC 33090 and Escherichia coli ATCC 25922 were performed. The growth of S. aureus and L. innocuastrain was not inhibited by b-casein; E. coli strain growth was slightly inhibited. All fractions of hydrolysatesexhibited some anti-bacterial activity and molecular mass fraction <1 kDa was the most activeagainst both Gram-positive bacterial strains. Mass spectrometry analysis revealed that this fractioncontained 129 peptides. Interestingly, 2 of them, f(193e204) and f(193e213), presented at least 50%homology with casecidins 15 and 17 from bovine b-casein. This is the first study reporting the presenceof two putative antibacterial fragments in camel b-casein peptic hydrolysate

COL1A1 C-propeptide mutations cause ER mislocalization of procollagen and impair C-terminal procollagen processing

International audienc