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.

Highlights

  • The MEROPS database, which is a manually curated information resource for proteolytic enzymes, their inhibitors and substrates, relocated to the EMBL-European Bioinformatics Institute (EMBL-EBI) during 2017

  • The hierarchical classification in MEROPS was established for peptidases in 1993 [1] and for peptidase inhibitors in 2004 [2]

  • Sequence analysis is restricted to that portion of the protein directly responsible for peptidase or inhibitor activity, which is termed the ‘peptidase unit’ or the ‘inhibitor unit’

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Summary

Introduction

If the sequence can be shown to be similar to those in an established family, the new MEROPS identifier will be an addition to that family. If the new activity cannot yet be associated with a protein sequence, a special MEROPS identifier is assigned in which the first character indicates the catalytic type, the second character is ‘9’, and the third character is a letter, depending on the type of proteolytic activity (A indicates an aminopeptidase, B is a dipeptidase, C is a dipeptidyldipeptidase, D is a peptidyl-dipeptidase, E is a carboxypeptidase, F is an omega peptidase, and G is an endopeptidase). The activity cannot be added to an existing family and new families cannot be assembled without a protein sequence, but action on substrates and interaction with inhibitors can be added to our data, which may help with identifying the source sequence in the future.

Results
Conclusion

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