Botos I, Scapozza L, Zhang D, Liotta L A, Meyer E F
Department of Biochemistry and Biophysics, Texas A&M University, College Station, 77843, USA.
Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2749-54. doi: 10.1073/pnas.93.7.2749.
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.
基质金属蛋白酶已被证实与肿瘤细胞侵袭、转移及关节炎等退行性病变过程有关。特异性金属蛋白酶抑制剂已被用于阻断肿瘤细胞增殖。我们以2.0埃的分辨率（R = 16.8%）研究了batimastat（BB - 94）与一种金属蛋白酶[Atrolysin C（Ht - d），EC 3.4.24.42]活性位点的相互作用。标题结构呈现出一种意想不到的结合几何形状，噻吩环深深插入主要特异性位点。这种前所未有的结合几何形状凸显了海绵状主要特异性位点的重要性，为新一代潜在抗肿瘤药物的设计指明了方向。
