1KBC

PROCARBOXYPEPTIDASE TERNARY COMPLEX

Summary for 1KBC

• Entry DOI: 10.2210/pdb1kbc/pdb
• Descriptor: NEUTROPHIL COLLAGENASE, CALCIUM ION, ZINC ION, ... (6 entities in total)
• Functional Keywords: hydrolytic enzyme, metalloproteinase, collagenase, matrixin, mmp-8, hnc, inhibitor, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasmic granule: P22894
• Total number of polymer chains: 2
• Total formula weight: 37742.87

Authors

Betz, M.,Gomis-Rueth, F.X.,Bode, W. (deposition date: 1997-04-29, release date: 1997-08-12, Last modification date: 2024-02-07)

Primary citation

Betz, M.,Huxley, P.,Davies, S.J.,Mushtaq, Y.,Pieper, M.,Tschesche, H.,Bode, W.,Gomis-Ruth, F.X.
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.
Eur.J.Biochem., 247:356-363, 1997

PubMed Abstract: 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.

PubMed: 9249047
DOI: 10.1111/j.1432-1033.1997.00356.x

Experimental method

X-RAY DIFFRACTION (1.8 Å)