MEROPS

An exopeptidase that sequentially releases an amino acid from the N-terminus of a protein or peptide. Examples include cystinyl aminopeptidase (MEROPS M01.011), which removes a terminal cysteine from the biologically important peptides oxytocin and vasopressin, and methionyl aminopeptidase (M24.001), which removes the initiating methionine from cytosolic... 

Cysteine endopeptidases Clan CD Family Cl 4 ( http //merops.sanger.ac.uk/)... 

An exopeptidase that can only degrade a dipeptide. Examples are carnosine dipeptidase I (MEROPS M20.006), which degrades carnosine (beta-Ala-His), and membrane dipeptidase (MEROPS Ml9.001), which is important in the catabolism of glutathione, degrading the dipeptides Cys-Gly. Dipeptidases are included in Enzyme Nomenclature sub-subclass 3.4.13. 

Peptidases have been classified by the MEROPS system since 1993 [2], which has been available viatheMEROPS database since 1996 [3]. The classification is based on sequence and structural similarities. Because peptidases are often multidomain proteins, only the domain directly involved in catalysis, and which beais the active site residues, is used in comparisons. This domain is known as the peptidase unit. Peptidases with statistically significant peptidase unit sequence similarities are included in the same family. To date 186 families of peptidase have been detected. Examples from 86 of these families are known in humans. A family is named from a letter representing the catalytic type ( A for aspartic, G for glutamic, M for metallo, C for cysteine, S for serine and T for threonine) plus a number. Examples of family names are shown in Table 1. There are 53 families of metallopeptidases (24 in human), 14 of aspartic peptidases (three of which are found in human), 62 of cysteine peptidases (19 in human), 42 of serine peptidases (17 in human), four of threonine peptidases (three in human), one of ghitamicpeptidases and nine families for which the catalytic type is unknown (one in human). It should be noted that within a family not all of the members will be peptidases. Usually non-peptidase homologues are a minority and can be easily detected because not all of the active site residues are conserved. 

Links are provided to the relevant summary pages in the MEROPS database. 

With the onset of genomic biology, there are now many sequences derived from genome sequencing projects that are too divergent to be considered species variants of known peptidases. Of the 54,124 sequences in the MEROPS database only 18,741 (34.6%) have been assigned to an identifier. 

Rawlings ND, Morton FR, Barrett AJ (2006) MEROPS the peptidase database. Nucleic Acids Res 34 D270-D272... 

An endopeptidase that is incapable of cleaving proteins but can cleave small peptides. An example is thimet oligopeptidase (MEROPS M03.001). 

An exopeptidase that does not cleave standard peptide bonds. An example is pyroglutamyl-peptidase I (MEROPS C15.010), which releases an N-terminal pyroglutamyl from hormones such as thyrotropinreleasing hormone and luteinizing hormone. Omega peptidases are included in Enzyme Nomenclature subsubclass 3.4.19. 

An exopeptidase that sequentially releases dipeptides from the C-terminus of a protein or peptide. An example is angiotensin-converting enzyme (also known as peptidyl-dipeptidase A MEROPS XM02-001), which plays an important role in the control of blood pressure by converting angiotensin I to angiotensin II. Peptidyl-dipeptidases are included in Enzyme Nomenclature sub-subclass 3.4.15. 

Merops (http //merops.sanger.ac.uk), database of peptidases and their proteinaceous inhibitors. Includes enzyme classification and nomenclature, external links to literature, and the structure of proteins of interest (if known). Enables one to find the gene coding for a given peptidase or to find the best enzyme to digest a chosen substrate. 

MEROPS database published by Rawlings et ai., 2004). Each of these has overlapping but distinct preferences for peptide bonds and, hence, together can affect the efficient breakdown of proteins. As cysteine proteases generally operate at slightly acid pH (5.0-6.5), they are suitable for functioning within the low pH of the gut lumen (for S. mansoni) where initial cleavage steps take place (Dresden et ai., 1981 Dalton et ai., 1996 Brindley et ai., 1997 Tort et ai., 1999 Sajid and McKerrow, 2002). 

Official gene name Other names/symbols Genbank accession number Unigene cluster Merops ID SwissProt ID... 

Merops Peptidases http //www.bi.bbsrc.ac.uk/Merops/Merops.htm... 

MDB Metalloenzymes Merops Peptidases PKR Protein kinase PlantsP Plant protein kinases phosphatase... 

European bee-eater (bird) (.Merops Bee venom suspected N.D. Gulbahar et al. (2003)... 

Gulbahar, O., Mete, N., Ardeniz, O., Onbasi, K., Kokuludag, A., Sin, A., and Sebik, F. 2003. Laryngeal edema due to European bee-eater (Merops apiaster) in a patient allergic to honeybee. Allergy 58(5) 453-453. 

An increasing emphasis on comparative genomics can be seen in the development of databases covering a broad spectrum of gene families, as well as specialist databases devoted to individual gene families (for example, the MEROPS protease database). 

Prior to the start of any experimental substrate finding activity, databases should be mined. A tremendous amount of information about proteases, substrates, inhibitors, and structures can be retrieved from two searchable databases MEROPS (Rawlings et al., 2006) (http //merops.sanger. ac.uk) and BRENDA (www.brenda-enzymes.de), that serve as good starting points for assay development in many cases. These databases are available to the public and should be consulted as primary sources of information. 

Barret, A.J. 2004. Bioinformatics of proteases in the MEROPS database. Cum Opin. Drug Disc. Dev. 7, 334-341. 

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