MEROPS: the peptidase database.

The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
Nucleic Acids Research (Impact Factor: 8.81). 02/2008; 36(Database issue):D320-5. DOI: 10.1093/nar/gkm954
Source: PubMed

ABSTRACT Peptidases (proteolytic enzymes or proteases), their substrates and inhibitors are of great relevance to biology, medicine and biotechnology. The MEROPS database ( aims to fulfil the need for an integrated source of information about these. The organizational principle of the database is a hierarchical classification in which homologous sets of peptidases and protein inhibitors are grouped into protein species, which are grouped into families and in turn grouped into clans. Important additions to the database include newly written, concise text annotations for peptidase clans and the small molecule inhibitors that are outside the scope of the standard classification; displays to show peptidase specificity compiled from our collection of known substrate cleavages; tables of peptidase-inhibitor interactions; and dynamically generated alignments of representatives of each protein species at the family level. New ways to compare peptidase and inhibitor complements between any two organisms whose genomes have been completely sequenced, or between different strains or subspecies of the same organism, have been devised.


Available from: Neil D Rawlings, May 29, 2015
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    DESCRIPTION: Moritella viscosa is the aetiological agent of winter ulcer disease in farmed salmonid fish. The disease has had significant economic effects on the salmon aquaculture industry in the North Atlantic, and continues to cause problems despite the availability of commercial vaccines. Infections also occur in cultured Atlantic cod (Gadus morhua L.). Improved understanding of M. viscosa, its biology, virulence mechanisms and host-pathogen interactions is therefore important in order to fight disease outbreaks and for development of effective treatments against the disease. The main objectives of this study were to examine the virulence mechanisms of M. viscosa, with emphasis on secreted factors and bacterial interactions with its host. In the first part of the study, the virulence properties of extracellular products (ECP) of 22 M. viscosa isolates were evaluated. The in vivo and in vitro virulence of ECPs were screened and several parameters measured. Virulent isolates produced an unidentified lethal factor and the results reflected the proposed significance ECP may have on the development and pathology of winter ulcer disease. Avirulent M. viscosa isolates produced non-lethal ECPs. Cytotoxin production followed host species origin of isolates and may reflect host adaptation in M. viscosa. Successively, the major extracellular caseinase of M. viscosa was isolated and characterized. The caseinase, termed MvP1, was a previously unknown vibriolysin with virulence related activities. The MvP1 peptidase, which was active over a broad temperature range, caused hemorrhages and tissue destruction in salmon and may aid in bacterial invasion and dissemination within the host. Attempts to construct MvP1 negative mutants were unsuccessful and the importance of this peptidase in M. viscosa virulence was therefore not fully determined. For evaluating the ability of M. viscosa to trigger a host immune response, selected M. viscosa antigens were used to stimulate a continuous salmon cell line. Following stimulation, expression of the IL-1β and IL-8 cytokine genes was measured, as indicators of a pro-inflammatory response. Live M. viscosa cells induced both IL-1β and IL-8 expression, while heat-killed cells and ECP only induced the expression of IL-8. Furthermore, isolated MvP1 was not a major stimulant of pro-inflammatory gene expression. The results indicate that M. viscosa antigens have different stimulatory potentials, which may be of value for improved vaccine production. Finally, two type VI secretion system (T6SS) loci were identified in the genome of M. viscosa, termed mts1 and mts2. A functional Mts1 system was confirmed in M. viscosa, both in virulent and avirulent isolates. T6SSs can export proteins through a needle like structure into the environment or directly into host cells, and they have been implicated with various functions, including virulence. However, the role of T6S in M. viscosa is yet unknown and is an interesting research topic. Overall, the results of the study give new insight into the biology and virulence of M. viscosa, especially into the importance of secreted factors on disease development. Keywords: Moritella viscosa, virulence, extracellular products, secretion, MvP1 peptidase
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    05/2011, Degree: PhD, Supervisor: Bjarnheidur K. Gudmundsdottir
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    ABSTRACT: Metalloproteins account for a substantial fraction of all proteins. They incorporate metal atoms, which are required for their structure and/or function. Here we describe a new computational protocol to systematically compare and classify metal-binding sites on the basis of their structural similarity. These sites are extracted from the MetalPDB database of minimal functional sites (MFSs) in metal-binding biological macromolecules. Structural similarity is measured by the scoring function of the available MetalS2 program. Hierarchical clustering was used to organize MFSs into clusters, for each of which a representative MFS was identified. The comparison of all representative MFSs provided a thorough structure-based classification of the sites analyzed. As examples, the application of the proposed computational protocol to all heme-binding proteins and zinc-binding proteins of known structure highlighted the existence of structural subtypes, validated known evolutionary links and shed new light on the occurrence of similar sites in systems at different evolutionary distances. The present approach thus makes available an innovative viewpoint on metalloproteins, where the functionally crucial metal sites effectively lead the discovery of structural and functional relationships in a largely protein-independent manner.
    Scientific Reports 03/2015; 5:9486. DOI:10.1038/srep09486 · 5.08 Impact Factor