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PDBsum entry 1kbc
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Metalloproteinase
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PDB id
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1kbc
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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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.
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Authors
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M.Betz,
P.Huxley,
S.J.Davies,
Y.Mushtaq,
M.Pieper,
H.Tschesche,
W.Bode,
F.X.Gomis-Rüth.
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Ref.
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Eur J Biochem, 1997,
247,
356-363.
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PubMed id
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Abstract
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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.
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