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. 1996 Apr 2;93(7):2749–2754. doi: 10.1073/pnas.93.7.2749

Batimastat, a potent matrix mealloproteinase inhibitor, exhibits an unexpected mode of binding.

I Botos 1, L Scapozza 1, D Zhang 1, L A Liotta 1, E F Meyer 1
PMCID: PMC39703  PMID: 8610113

Abstract

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), EC 3.4.24.42] active site at 2.0-angstroms 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.

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