The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family.

摘要: The general applicability of the "cysteine-switch" activation mechanism to members matrix metalloproteinase (MMP) gene family is examined here. All currently known MMP share characteristic that they are synthesized in a latent, inactive, form. Recent evidence suggests this latency human fibroblast collagenase (HFC) result formation an intramolecular complex between single cysteine residue its propeptide domain and essential zinc atom catalytic domain, blocks active site. Latent HFC can be activated by multiple means, all which effect dissociation from complex. This referred as activation. contains critical zinc-binding site only two domains common MMPs. amino acid sequences surrounding both region protein chains containing putative histidine ligands highly conserved A survey literature shows many individual MMPs means observed for latent HFC. These observations support view cysteine-switch applicable family. unprecedented enzymology far we know offers opportunity modes physiological these important enzymes. Since conditions different cells tissues may match those necessary one given MMP, offer metabolic flexibility control