MEROPS is an

online database An online database is a database accessible from a local network or the Internet, as opposed to one that is stored locally on an individual computer or its attached storage (such as a CD). Online databases are hosted on websites, made available as s ...

for peptidases (also known as

proteases A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the for ...

proteinases A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

and

proteolytic enzymes Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...

) and their inhibitors. The

classification scheme In information science and ontology, a classification scheme is the product of arranging things into kinds of things (classes) or into ''groups'' of classes; this bears similarity to categorization, but with perhaps a more theoretical bent, as cla ...

for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibitors by Rawlings ''et al.'' in 2004.Rawlings, N.D., Tolle, D.P. & Barrett, A.J. (2004) "Evolutionary families of peptidase inhibitors." ''Biochem J'' 378, 705-716. The most recent version, MEROPS 12.3, was released in September 2020.

Overview

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

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...

, and for a protein inhibitor the reactive site. The classification is hierarchical: sequences are assembled into families, and families are assembled into clans. Each peptidase, family, and clan has a unique identifier.

Classification

Family

The families of peptidases are constructed by comparisons of amino acid sequences. 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 FASTA is a DNA and protein sequence alignment software package first described by David J. Lipman and William R. Pearson in 1985. Its legacy is the FASTA format which is now ubiquitous in bioinformatics. History The original FASTA program ...

or BlastP is used to establish sequence relationships, with an expect value of 0.001 or lower taken to be

statistically significant In statistical hypothesis testing, a result has statistical significance when it is very unlikely to have occurred given the null hypothesis (simply by chance alone). More precisely, a study's defined significance level, denoted by \alpha, is the p ...

HMMER HMMER is a free and commonly used software package for sequence analysis written by Sean Eddy. Its general usage is to identify homologous protein or nucleotide sequences, and to perform sequence alignments. It detects homology by comparing ...

or psi-blast searches are used for adding sequences which are distantly related to a family. Each family is identified by a letter representing the catalytic type of the peptidases it contains followed by an arbitrary unique number. Some families are divided into subfamilies due to evidence of very ancient divergence within the family. The divergence corresponds to more than 150 accepted point mutations per 100 amino acid residues.

Clan

The similarity in three-dimensional structures supports the evidence that many of the families do share common ancestry with others. "Clan" is used to describe such a group of families. 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

tertiary structure Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may int ...

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 In statistics, the standard score is the number of standard deviations by which the value of a raw score (i.e., an observed value or data point) is above or below the mean value of what is being observed or measured. Raw scores above the mean ...

of 6.00

standard deviation In statistics, the standard deviation is a measure of the amount of variation or dispersion of a set of values. A low standard deviation indicates that the values tend to be close to the mean (also called the expected value) of the set, while ...

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.

Identifier

Each family, clan, peptidase, and inhibitor has a unique identifier. Description and example of identifiers are shown in the table below.

References

External links

MEROPS database
{{Wellcome Trust Biological databases Proteases Protein classification Proteomics organizations Science and technology in Cambridgeshire South Cambridgeshire District Wellcome Trust