Twenty years of the MEROPS database of proteolytic enzymes, their substrates and inhibitors

Abstract

The MEROPS database (http://merops.sanger.ac.uk) is an integrated source of information about peptidases, their substrates and inhibitors, which are of great relevance to biology, medicine and biotechnology. The hierarchical classification of the database is as follows: homologous sets of sequences are grouped into a protein species; protein species are grouped into a family; families are grouped into clans. There is a type example for each protein species (known as a 'holotype'), family and clan, and each protein species, family and clan has its own unique identifier. Pages to show the involvement of peptidases and peptidase inhibitors in biological pathways have been created. Each page shows the peptidases and peptidase inhibitors involved in the pathway, along with the known substrate cleavages and peptidase-inhibitor interactions, and a link to the KEGG database of biological pathways. Links have also been established with the IUPHAR Guide to Pharmacology. A new service has been set up to allow the submission of identified substrate cleavages so that conservation of the cleavage site can be assessed. This should help establish whether or not a cleavage site is physiologically relevant on the basis that such a cleavage site is likely to be conserved.

Figure 1.

An example of a biological pathway page. The page displaying peptidases and peptidase inhibitors involved in the blood coagulation and complement activation pathway is shown. Only part of each table is shown.

Figure 2.

An example of results returned by the substrate analysis service. Alignment of homologues of alpha-2-antiplasmin showing cleavage at residue 30 by fibroblast activation protein alpha subunit (S09.007). This is the fifth result from the list shown above. The known cleavage occurs in the human protein (UniProt: P08697; 27) and is highlighted in green. Four residues either side of the cleavage site are highlighted. A conserved residue is highlighted in pink. A residue that differs from that in the human sequence is highlighted in orange if the same amino acid is known to occupy the same binding site from another substrate of this peptidase; and in black if the amino acid is not known to occur in the same binding site from any substrate for this peptidase. The high number of residues highlighted in black indicates that this cleavage is unlikely to be physiologically relevant, but note that the number of cleavages known for this peptidase is low.