Databases MEROPS

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. 

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... 

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). 

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). 

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

Merops database, http //www.MEROPS.Sanger.Ac.Uk.code SO 1.217... 

Over 90 phylogenetically distinct families of protease inhibitors have been classified by the MEROPS database. We will focus the current discussion on the most abundant and well-characterized groups. 

The MEROPS database of peptidases and inhibitors is an invaluable resource that can be found at http //merops.sanger.ac.uk/... 

In addition to the above mentioned databases that try to cover the entire world of enzymes, there are a number of more topical databases focusing on particular enzyme families. The MEROPS database, maintained at the Babraham Institute in Cambridge, provides a catalog and a structure-based classification scheme for all proteolytic enzymes 58. In addition to the classification, the database also provides a digest of published information on the peptidases as well as dadograms and multiple sequence alignments of the peptidase families. 

Among the prokaryotic organisms, peptidases of seven catalytic types are found. Only one, the glutamic peptidase, has been recently described in prokaryotes in the thermoacidophilic bacteria Alicyclobacillus sp. DSM 15716 (Jensen et al. 2010). In the next section, some peptidases from the different catalytic types will be cited below, but the peptidases fi-om prokaryote can be found in MEROPS database (Rawlings et al. 2010). 

In Merops, the peptidase database, release 9.5, there are 16 families of the aspartic peptidases distributed between vertebrates, fungi, plants, protozoa, viruses, and prokaryotes (Horimoto et al. 2009). Structurally, aspartic peptidases are bilobal enzymes, each lobe contributing with a catalytic Asp residue, with an extended active site cleft localized between the two lobes of the molecule. The presence and position of disulfide bridges are another conserved feature of aspartic peptidases. All or most aspartate peptidases are endopeptidases. In prokaryotes, they are detected in archaea and bacteria. One example is the thermopsin, which is a thermostable acid protease fi-om the archaea Sulfolobus acidocaldarius (A5 family, EC 3.4.23.42) (Dash et al. 2003). The enzyme shows a broad protein substrate... 

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