The MEROPS database of proteolytic enzymes, their substrates and inhibitors in 2017 and a comparison with peptidases in the PANTHER database

Abstract

The MEROPS database (http://www.ebi.ac.uk/merops/) is an integrated source of information about peptidases, their substrates and inhibitors. The hierarchical classification is: protein-species, family, clan, with an identifier at each level. The MEROPS website moved to the EMBL-EBI in 2017, requiring refactoring of the code-base and services provided. The interface to sequence searching has changed and the MEROPS protein sequence libraries can be searched at the EMBL-EBI with HMMER, FastA and BLASTP. Cross-references have been established between MEROPS and the PANTHER database at both the family and protein-species level, which will help to improve curation and coverage between the resources. Because of the increasing size of the MEROPS sequence collection, in future only sequences of characterized proteins, and from completely sequenced genomes of organisms of evolutionary, medical or commercial significance will be added. As an example, peptidase homologues in four proteomes from the Asgard superphylum of Archaea have been identified and compared to other archaean, bacterial and eukaryote proteomes. This has given insights into the origins and evolution of peptidase families, including an expansion in the number of proteasome components in Asgard archaeotes and as organisms increase in complexity. Novel structures for proteasome complexes in archaea are postulated.

Figure 1.

An example peptidase summary page showing cross-references to external databases. The page displaying the summary for cathepsin B is shown and includes cross-references to the Enzyme Nomenclature, TreeFam and PANTHER databases.

Figure 2.

Examples of proteasome complexes. Schematic representations of proteasome complexes from selected organisms are shown. The predicted relationship between the organisms is shown as a simplified phylogenetic tree at the left of the figure. The symmetry of each ring, ring composition and structure of the complexes are shown; these are hypothetical for proteasomes from Pyrococcus, Sulfolobus and the Lokiarchaeote. Homologues of peptidase family T1 are shown as filled spheres: alpha subunits are shown in shades of blue, and beta subunits in shades of green (proteolytically active subunits) and grey (proteolytically inactive). The unrelated HslU subunits are shown as orange spheres.