Sandbox Reserved 1125: Difference between revisions

The cleavage is at Gly775–Ile776 or Leu776 in each alpha-chain of the collagen molecule<ref>PMID:9094424</ref> and takes place at neutral pH. It generates fragments that spontaneously lose their helical conformation, denature to gelatin, and become soluble. The gelatin is then susceptible to attack by gelatinases and other proteases.<ref>[http://www.ebi.ac.uk/interpro/entry/IPR028709 "Neutrophil collagenase"]</ref>

Petites info Chrichri:

<font color='red'>MMP activity may subsequently be regulated by the action of inhibitors, notably the tissue inhibitors of MMPs (TIMPs) - TIMP-1, TIMP-2, TIMP-3 and TIMP-4 - and the serum panproteinase inhibitor α2 macroglobulin (Baker et al., 2002) The TIMPs are six-loop disulphide-bonded proteins forming two domains. They interact via their N-terminal three disulphide-bonded loops with the active site cleft of the catalytic domain, although significant interactions of the hemopexin-like domains of MMP-2 and MMP-9 with the C-terminal domains of TIMPs appear to have specific biological relevance. The other MMP domains have distinct functions, such as as exosites for substrate interactions, e.g. the hemopexin-like domains of MMP-1, MMP-8, MMP-13, MMP-14, MMP-16 and MMP-18 are essential for their ability to cleave fibrillar collagens and the fibronectin-like domains of MMP-2 and MMP-9 confer their binding to denatured collagen substrates. The hemopexin-like domain of MMP-14 can homodimerise in order to promote its clustering at the cell surface, a property that promotes its activity. The hemopexin-like domain confers the ability to interact with other extracellular matrix components and cell adhesion molecules and may be of significance in the determination of specific pericellular locations of individual MMPs.

Overexpression of MMP-8, or inadequate control by TIMPs, can be associated with a lot of pathological conditions: psoriasis, sclerosis, osteoarthritis, rheumatoid arthritis, osteoporosis, Alzheimer's disease, tumor growh and metastasis.<ref>[http://www.enzim.hu/~lbarna/articles/19173605.pdf "Extra Binding Region Induced by Non-Zinc Chelating Inhibitors into the S1′ Subsite of Matrix Metalloproteinase 8"]</ref>

Neutrophil collagenase or collagenase 2 (MMP-8) is unique among the family of matrix metalloproteinases (MMPs) because of its exclusive pattern of expression in inflammatory conditions.<ref>PMID:9727011</ref>

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