The MEROPS database of proteolytic enzymes, their substrates and inhibitors provides a "one-stop shop" for researchers with an interest in proteolytic enzymes. The aim of the database is to provide a classification, a software interface and a bibliography for the retrieval of information about proteolytic enzymes, their substrates and inhibitors, and for the analysis of sequence data. A proteolytic enzyme catalyses the cleavage of a peptide or protein by breaking the peptide bond that exists between amino acids in the chain. The MEROPS classification for peptidases began in 1993. Sequences are grouped into a protein species if they represent the same protein but from different species. For each protein species a type example or holotype is selected, which is usually the protein for which most biochemistry is known. Protein species are grouped into a family if the sequences can be shown to be homologous. Sequence homology can be shown by means of software such as FastA, BlastP and HMMER; to be included in a family a sequence must match an existing member of the family with an expect value of less than 0.001. Because the MEROPS system is a domain classification, the sequence relationship must be within the region identified as the peptidase domain, known as the "peptidase unit". Families are grouped into a clan if the proteins within them share a similar structural fold.
The classification was extended to peptidase inhibitors in 2004. There are six different catalytic types of peptidase, depending on the nature of the nucleophile in the catalytic reaction. Peptidases that use the hydroxyl or thiol group of an amino acid as a nucleophile are known as serine, threonine or cysteine peptidases. Peptidases that use an activated water molecule to hydrolyse a peptide bond are known as aspartic, glutamic or metallo- peptidases, depending on whether the water molecule is bound to aspartic or glutamic acid residues, or to a metal ion. In addition to the peptidases that cleave a peptide bond by hydrolysis, there are also peptide lyases, in which a peptide bond is broken because an asparagine or glutamine residue undergoes a cyclization reaction. There is a unique name for every protein species, family and clan in MEROPS. The first letter of each of these corresponds to the catalytic type: A for aspartic peptidase, C for cysteine peptidase, G for glutamic peptidase, M for metallopeptidase, S for serine peptidase and T for threonine peptidase. In addition, the letter "P" is used for peptidases of mixed catalytic type; the letter "U" is used for peptidases where the catalytic type cannot be determined or is ambiguous; the letter "N" is used for peptide lyases; and the letter "I" is used for peptidase inhibitors.
All proteins are subject to proteolysis, either as a means of activation, de-activation or degradation. In addition to the nomenclature and classification of proteolytic enzymes and peptidase inhibitors, the MEROPS database is also a repository for the known cleavages in peptide, protein and synthetic substrates.
The MEROPS database is also a repository for peptidase-inhibitor interactions. We also a maintain a collection of small-molecule inhibitors, which include naturally occurring and synthetic inhibitors, many of which have important uses in peptidase biochemistry and pharmacology.
In the current release, there are over 500,000 sequences, over 4,600 different peptidases, over 700 different peptidase inhibitors, over 64,000 substrate cleavages, over 6,000 peptidase/inhibitor interactions, and over 59,000 references.
We provide a service analyse sequences and to identify any peptidases or peptidase inhibitors. A user can upload a library of sequences in FastA format and will receive by E-mail a list of peptidase homologues with the MEROPS family and active site residues identified. This service is useful for identifying peptidases in a complete proteome.
We also provide a service to analyse cleaves in proteins to see if the cleavage site is conserved in close homologues. This service is useful for identifying physiologically important cleavages, because these are most likely to be well conserved.