How to use the MEROPS database and website to help understand peptidase specificity.

The MEROPS website (https://www.ebi.ac.uk/merops) and database was established in 1996 to present the classification and nomenclature of proteolytic enzymes. This was expanded to include a classification of protein inhibitors of proteolytic enzymes in 2004. Each peptidase or inhibitor is assigned to a distinct identifier, based on its biochemical and biological properties, and homologous sequences are assembled into a family. Families in which the proteins share similar tertiary structures are assembled into a clan. The MEROPS classification is thus a hierarchy with at least three levels (protein-species, family and clan) showing the evolutionary relationship. Several other data collections have been assembled which are accessed from all levels in the hierarchy. These include, sequence homologues, selective bibliographies, substrate cleavage sites, peptidase-inhibitor interactions, alignments and phylogenetic trees. The substrate cleavage collection has been assembled from the literature and includes physiological, pathological and non-physiological cleavages in proteins, peptides and synthetic substrates. In this article we make recommendations about how best to analyse these data, and show analyses to indicate peptidase binding site preferences and exclusions. We also identify peptidases where co-operative binding occurs between adjacent binding sites. This article is protected by copyright. All rights reserved.