Batimastat, a Potent Matrix Metalloproteinase Inhibitor, Exhibits an Unexpected Mode of Binding

Matrix metalloproteinase enzymes have been implicated in degenerative processes like tumor cell invasion, metastasis, and arthritis. Specific metalloproteinase inhibitors have been used to block tumor cell proliferation. We have examined the interaction of batimastat (BB-94) with a metalloproteinase...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-04, Vol.93 (7), p.2749-2754
Main Authors: Botos, Istvan, Scapozza, Leonardo, Zhang, Dachuan, Liotta, Lance A., Meyer, Edgar F.
Format: Article
Language:English
Subjects:
Active sites
Atoms
Binding sites
Biochemistry
Enzymes
Ligands
Molecules
Oxygen
Thiophenes
Tumors
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Summary:Matrix metalloproteinase enzymes have been implicated in degenerative processes like tumor cell invasion, metastasis, and arthritis. Specific metalloproteinase inhibitors have been used to block tumor cell proliferation. We have examined the interaction of batimastat (BB-94) with a metalloproteinase [atrolysin C (Ht-d), EC3.4.24.42] active site at 2.0- angstrom resolution (R = 16.8%). The title structure exhibits an unexpected binding geometry, with the thiophene ring deeply inserted into the primary specificity site. This unprecedented binding geometry dramatizes the significance of the cavernous primary specificity site, pointing the way for the design of a new generation of potential antitumor drugs.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.7.2749