MEROPS is an on-line Wikipedia:database for peptidases (also known as Wikipedia:proteases) and their inhibitors. The Wikipedia:classification scheme for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibitors by Rawlings et al. in 2004.
The classification is based on similarities at the tertiary and primary structural levels. Comparisons are restricted to that part of the sequence directly involved in the reaction, which in the case of a peptidase must include the Wikipedia:active site, and for a protein inhibitor the reactive site. The classification is hierarchical: sequences are assembled into families, and families are assembled into clans. A family is assembled around a type example, the sequence of a well-characterized peptidase or inhibitor. All other sequences in the family must be related to the family type example, either directly or through a transitive relationship involving one or more sequences already shown to be family members. Typically, FastA or BlastP are used to establish sequence relationships, with an expect value of 0.001 or lower taken to be statistically significant. A clan is also assembled around a type example, this being the structure of a well-characterized peptidase or inhibitor. A family is included in a clan if the Wikipedia:tertiary structure of a family member can be shown to be related to that of the clan type example. Typically, DALI is used to establish clan membership, with a z score of 6.00 Wikipedia:standard deviation units or above considered to be statistically significant. For peptidases, other evidence to indicate that families are related when a tertiary structure is absent includes the same order of catalytic residues in the sequences.
- Rawlings, N.D., Morton, F.R. & Barrett, A.J. (2006) MEROPS: the peptidase database. Nucleic Acids Res 34, D270-D272.
- Rawlings, N.D. & Barrett, A.J. (1993) Evolutionary families of peptidases. Biochem J 290, 205-218.
- Rawlings, N.D., Tolle, D.P. & Barrett, A.J. (2004) Evolutionary families of peptidase inhibitors. Biochem J 378, 705-716.