MEROPS protease database

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). 

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). 

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. 

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. 

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... 

Peptidases or proteases are enzymes that hydrolyse peptide bonds [9]. Proteolytic enzymes can be classified in five classes on basis of their catalytic mechanism aspartic, metallo-, cysteine, threonine and serine peptidases, whereby the latter three follow the same basic mechanism (Scheme 7.3) [10], Another classification of peptidases on the basis of statistically significant similarities in amino acid sequences was presented by Rawlings et al. (MEROPS database) [11], Serine proteases (SP) alone cover approximately one-third of all known proteases, and can accelerate the peptide hydrolysis very efficiently 10 fold) [6,11,12], SPs also hydro-... 

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