Structure determination and analysis of human neutrophil collagenase complexed with a hydroxamate inhibitor

摘要: Matrix metalloproteinases are a family of zinc endopeptidases involved in tissue remodeling. They have been implicated various disease processes including metastasis, joint destruction, and neurodegeneration, Human neutrophil collagenase (HNC, MMP-8) represents one the three ''interstitial'' collagenases that cleave triple-helical collagens types I, II, III. Its 163-residue catalytic domain (Met80 to Gly242) has expressed Escherichia coli crystallized as noncovalent complex with hydroxamate inhibitor batimastat. The crystal structure, refined 2.1 Angstrom, demonstrates batimastat binds S1-S2' sites coordinates bidentate manner via hydroxyl carbonyl oxygens group. batimastat-collagenase is described detail, activities analogues discussed light protein-inhibitor interactions revealed by crystallography studies,