Metallo peptidase

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. 

MA M10 M10.003 Matrix metallo peptidase-2 Drug target for prevention of pathological tissue damage... 

Redmond, D.L., Knox, D.P., Newlands, G.F.J. and Smith, W.D. (1997) Molecular cloning of a developmentally regulated putative metallo-peptidase present in a host protective extract of Haemonchus contortus. Molecular and Biochemical Parasitology 85, 77-87. 

Volume 248. Proteolytic Enzymes Aspartic and Metallo Peptidases Edited by Alan J. Barrett... 

The peptidases were separated into catalytic types according to the chemical nature of the group responsible for catalysis. The major catalytic types are, thus, Serine (and the related Threonine), Cysteine, Aspartic, Metallo, and As-Yet-Unclassified. An in-depth presentation of catalytic sites and mechanisms, based on this classification, is the subject of Chapt. 3. 

Replacement of the peptide bond by a thioester group has been extensively applied in synthetic peptides used as enzyme substrates. Several classes of enzymes such as serine peptidases and metallo-endopeptidases are able to cleave efficiently thioester-modified amino acids and peptides. 61... 

Takahashi, K. (1995). Proteinase A from Aspergillus niger. In Barrett, A. J. (Ed). Methods in ENZYMOLOGT, Vol. 248. Proteolytic Enzymes Aspartic and Metallo Peptidases, (pp. 146-155.). New York Academic Press. 

Figure 7. Complete proteolytic stability of all types of P-and y-peptides towards a variety of peptidases. The P-peptides ranged in size from dimer to ISmer. The enzymes include all common types of peptidases (endo/exo, metallo, serine, threonine, and aspartyl proteases). After 40 hours there was no observable cleavage of any of the homologated peptides and no inhibition of the enzymes [41].

Figures 15.19-15.32 list examples of analogs of peptidyl transition states that have been employed to develop inhibitors of four classes of peptidases (81,82). These units are used to replace the scissile amide bond in a substrate sequence with either an amino acid or dipeptide isostere, or with a chelating moiety in the case of metallo peptidases. The...

Peptidylphosphonates have been demonstrated to mimic effectively the transition state involved in the enzymatic hydrolysis of the peptide bond, and are commonly used as inhibitors of peptidases, and in particular of metallo-proteases [146], A solid-phase method for the introduction of the (/[P0(0Me)0] motif exploits a modified Mitsunobu reaction (Scheme 7.11) [147]. 

Intracellular acid proteinase(s) and exopeptidases (amino and carboxy) have been found in P. roqueforti and P. camemberti but have not been well studied (see Gripon et al, 1991 Gripon, 1993). P. roqueforti excretes a carboxypeptidase with an acid pH optimum and an alkaline metallo amino-peptidase (see Gripon et al, 1991 Gripon, 1993). 

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