Endopeptidases extracellular

Thermolysin is a metalloenzyme isolated from Bacillus thermoproteo-lyticus. It is a heat-stable extracellular endopeptidase of molecular weight 34,600. The enzyme catalyzes the hydrolysis of peptide bonds that have the amino group as part of hydrophobic residues such as phenylalanine, isoleucine, or leucine. 

The matrix metalloproteinases (MMPs) are a large family of endopeptidases, responsible for degradation of a variety of extracellular matrix components in both normal tissue remodeling and pathological states [47]. The active site is a cavity spanning the entire enzyme, with three subsites on each side of the scissile bond (S3-S3, see Fig. 3.14). Most of the known MMP inhibitors so far exert their function by coordinating to residues in the primed side [48], only little effort has been put into exploring the unprimed sites [49, 50]. 

The matrix metalloproteinases (MMPs) are a family of calcium- and/or zinc-dependent endopeptidases involved in degradation of extracellular matrix and tissue remodelling (7). At least 21 mammalian MMPs have been described. They participate in various biological processes, such as embryonic development, ovulation, angiogenesis, apoptosis, wound heahng, and nerve growth. 

The BNP receptor is the extracellular domain of type A guanylyl cyclase, GC-A. The active receptor-cyclase complex is a homodimer. Activation of GC-A by nesiritide (BNP) increases cyclic GMP content in target tissues, including vascular, endothelial, and smooth muscle cells. As with nitrova-sodilators, elevated cyclic GMP leads to relaxation of vascular smooth muscle and vasodilation in both the venous and arterial systems. BNP is metabolized by specific clearance receptors, which facilitate its internalization and enzymatic degradation. It is also inactivated by neutral endopeptidases (NEP). Dose adjustment is not required in patients with renal dysfunction. 

V8 protease, EC 3.4.21.19, Endoproteinase Glu-C, protease I, protease type XVII-B, an extracellular endopeptidase from the V8 strain of Staphylococcus aureus. It cleaves peptide bonds on the C-terminal side of glutamic acid and, to a lesser extent, of aspartic acid. The X-ray crystallographic structure of V8 protease was described in 2004 [G. R. Drapeau et al., J. Biol. Chem. 1972, 247, 6720 L. Prasad et al, Acfa Crystallogr. 2004, D60, 256]. 

Botulism, a neuroparalytic life-threatening disease, is caused by the botulinum neurotoxin serotype A (BoNTA). Although antibodies are effective in preventing the extracellular toxin to continue the intoxication process, they have no effect on prior intoxicated neurons. Targeting the BoNTA endopeptidase (BoNTAe) could be a valid alternative, since its inhibition may potentially neutralize the intracellular BoNTA. 

Metalloproteinases especially matrix metalloproteinases are a group of endopeptidases that contribute for the extracellular matrix degradation, and several tissue remodeling processes. Improper regulation of these endopeptidases could lead to several severe pathological problems that include cardiac, cartilage, and cancer-related diseases. Until now, many synthetic matrix metalloproteinase inhibitory substances (MMPIs) have been reported however, many of them could not make to the final clinical trials. 

Matrix metalloproteinases (MMPs) are a family of extracellular zinc-dependent endopeptidases that hydrolyze the extracellular matrix and other extracellular proteins (Malemud, 2006). These enzymes are involved in both injury and repair mechanisms in brain and spinal cord. Three members of the MMP family, MMP-2,... 

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