MEROPS: the peptidase database

Abstract

Peptidases (proteolytic enzymes or proteases), their substrates and inhibitors are of great relevance to biology, medicine and biotechnology. The MEROPS database (http://merops.sanger.ac.uk) 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.

Figure 1.

Cleavage site sequence logo showing specificity for caspase-3. Amino acids preferred in positions P4–P4′ are shown in single-letter code. The specificity is shown as a string where each position is separated by a forward slash character and multiple letters in a position indicate a wide specificity for these amino acids. The scissile bond is shown by a red cross symbol. In the diagram, the height of the letter is proportional to the number of cleavage sites in which it is present. Positions P4–P4′ are numbered one to eight, with the scissile bond between residues four and five. Caspase-3, like most caspases, has a preference for Asp in P1 and a majority of substrates also have Asp in P4.

Figure 2.

Example SMI page. The summary page for the inhibitor pepstatin is shown.

Figure 3.

Peptidase–inhibitor interactions for aprotinin.

Figure 4.

Comparison between the peptidase complements of the human and the C. albicans genomes. Only the top and bottom portions of the table are shown.