Proteinases metalloproteinase

Microbial proteinases can be classified by mechanism of action. Hartley (1960) divided them into four groups serine proteinases, thio proteinases, metalloproteinases, and acid proteinases. Morihara (1974) classified enzymes within these groups according to substrate specificity. Enzymes which split peptide substrates at the carboxyl side of specific amino acids are called carboxyendopeptidases, and those which split peptide substrates at the amino side of specific amino acids are called aminoendopeptidases. Acid proteinases, such as rennin and pepsin, split either side of specific aromatic or hydrophobic amino acid residues. The action of proteolytic enzymes on milk proteins has been reviewed by Visser (1981). 

Metalloproteinases are a subgroup of proteinases. They are responsible for the cleavage of peptide bonds within a protein (proteolysis). Metalloproteinases contain a metal ion in the active center and are divided into four subclasses dependent on their mechanism of catalysis. 

Moss ML, Jin SL, MiUa ME et al (1997) Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature 385 733-736 Nixon RA, Cataldo AM (2006) Lysosomal system pathways genes to neurodegeneration in Alzheimer s disease. J Alzheimers Dis 9 277-289 Noorbakhsh F, VergnoUe N, HoUenberg MD et al (2003) Proteinase-activated receptors in the nervous system. Nat Rev Neurosci 4 981-990... 

Desrochers, P.E. and Weiss, S.J. (1988). Proteolytic inactivation of alpha-l-proteinase inhibitor by a neutrophil metalloproteinase. J. Clin. Invest. 81, 1646-1650. 

Removal of the N- and C-terminal propeptides from fully folded procollagens occurs only after transport of procollagens across the Golgi stacks and results in collagen molecules that are then able to assemble into fibrils. C-proteinase activity is possessed by members of the tolloid family of zinc metalloproteinases,... 

Penicillium caseicolum produces an extracellular aspartyl proteinase and a metalloproteinase with properties very similar to those of the extracellular enzymes produced by P roqueforti (Trieu-Cout and Gripon 1981 Trieu-Cout et al. 1982). Breakdown of casein in mold-ripened cheese results from the synergistic action of rennet and the proteases of lactic streptococci and penicillia (Desmazeaud and Gripon 1977). Peptidases of both lactic acid bacteria and penicillia contribute to formation of free amino acid and nonprotein nitrogen (Gripon et al. 1977). 

There are four basic mechanistic classes of enzyme which catalyse the hydrolysis of peptide bonds serine proteinases such as trypsin and chymo-trypsin, cysteine proteinases such as papain, acid (aspartic) proteinases such as pepsin, and zinc-containing metalloproteinases such as carboxypeptidase. X-ray crystal structures of representative examples of each class of enzyme are available, and the detailed reaction pathways probably taken by all four classes of enzyme have been subject to analysis in terms of ALPH, These analyses have been for the most part permissive rather than compelling, and are considered in turn below. 

Utility Proteinase Inhibitors for Treatment of Matrix Metalloproteinase... 

Zymography A method for detecting enzyme activity on a matrix, usually a polyacrylamide gel or agarose gel after electrophoretic separation. See Frederiks, W.M. and Mook, O.R., Metabolic mapping of proteinase activity with emphasis on in situ zymography of gelatinases review and protocols, J. Histochem. Cytochem. 52, 711-722, 2004 Lombard, C., Saulnier, J., and Wallach, J., Assays of matrix metalloproteinases (MMPs) activities a review, Biochemie 87, 265-272, 2005. 

Encron rizolipasc. endogenous pyrogen > interleukin-1. ENDOPEPTIDASE INHIBITORS act at one or other of the endopeptidase enzymes that cleave the C-terminal residue from oligopeptides or proteins (thus are stricdy proteinases). They can be divided into classes on the basis of their functional characteristics. These classes are dealt with separately in terms of their alternate names, notable substrates and inhibitors. They often act along with ectopeptidases - the carboxypeptidases and amino-peptidases. Endopeptidase inhibitors contain members of the metalloproteinase and serine protease families. Some are important neuropeptidases - concerned with degradation of... 

Cawston.T.E. (1995) Proteinases and Inhibitors. Br. Med. Bull.. 51. 385-401. Murphy. G. (1995) Matrix metalloproteinases and their inhibitors. Acta Orthop. Scand. Suppi.. 266.55-60. 

There are four main types of proteinases (a) serine proteinases that contain a serine residue at the active site, the hydroxy group of which has enhanced nucleophilicity, and the substrate acylates this residue with simultaneous liberation of the amino component of the peptide bond that is cleaved by the proteinase (b) cysteine proteinases that contain a cysteine residue at the active centre and the thiol group undergoes intermediate formation of an S-acyl intermediate similar to principle to the mechanism undergone by serine proteinases (c) aspartate proteinases that contain aspartic acid residues at the active site and (d) metalloproteinases that contain a zinc cation coordinated to the side-chains of amino acids such as aspartic acid and histidine. 

---