1kbc

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==Overview==
==Overview==
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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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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 Structure==
==About this Structure==
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[[Category: Betz, M.]]
[[Category: Betz, M.]]
[[Category: Bode, W.]]
[[Category: Bode, W.]]
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[[Category: Gomis-Rueth, F.X.]]
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[[Category: Gomis-Rueth, F X.]]
[[Category: CA]]
[[Category: CA]]
[[Category: HLE]]
[[Category: HLE]]
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[[Category: mmp-8]]
[[Category: mmp-8]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:12:14 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:32:10 2008''

Revision as of 11:32, 21 February 2008


1kbc, resolution 1.8Å

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PROCARBOXYPEPTIDASE TERNARY COMPLEX

Overview

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 Structure

1KBC is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Neutrophil collagenase, with EC number 3.4.24.34 Full crystallographic information is available from OCA.

Reference

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

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