1kbc
|
PROCARBOXYPEPTIDASE TERNARY COMPLEX
OverviewOverview
Matrix metalloproteinases (MMP) are zinc endopeptidases involved in tissue, remodelling. They have been implicated in a series of pathologies, including cancer, arthritis, joint destruction and Alzheimer's disease., Human neutrophil collagenase represents one of the three interstitial, collagenases that cleave triple-helical collagen of type I, II and III., Its catalytic domain (residues Phe79-Gly242) has been heterologously, expressed in Escherichia coli and crystallized as a non-covalent complex, with the hydroxamate inhibitor BB-1909, which has distinct selectivity, against different MMP, in a crystal form. The crystal structure, refined, to 0.18-nm resolution, shows that BB-1909 is a right-hand-side inhibitor, that binds to the S1'-S3' subsites and coordinates to the catalytic Zn2+, in a bidentate manner via the hydroxyl and carbonyl oxygen atoms of the, hydroxamate group in a similar manner to batimastat. The, collagenase/BB-1909 complex is described in detail and compared with the, collagenase/batimastat complex. These studies provide information on MMP, specificity and thus may assist the development of more-selective MMP, inhibitors.
About this StructureAbout this Structure
1KBC is a Single protein structure of sequence from Homo sapiens with CA, ZN and HLE as ligands. Active as Neutrophil collagenase, with EC number 3.4.24.34 Full crystallographic information is available from OCA.
ReferenceReference
1.8-A crystal structure of the catalytic domain of human neutrophil collagenase (matrix metalloproteinase-8) complexed with a peptidomimetic hydroxamate primed-side inhibitor with a distinct selectivity profile., Betz M, Huxley P, Davies SJ, Mushtaq Y, Pieper M, Tschesche H, Bode W, Gomis-Ruth FX, Eur J Biochem. 1997 Jul 1;247(1):356-63. PMID:9249047
Page seeded by OCA on Mon Nov 12 17:49:38 2007