Alterio Vincenzo, De Simone Giuseppina, Monti Simona Maria, Scozzafava Andrea, Supuran Claudiu T
Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Naples, Italy.
Bioorg Med Chem Lett. 2007 Aug 1;17(15):4201-7. doi: 10.1016/j.bmcl.2007.05.045. Epub 2007 May 18.
Three benzene-1,3-disulfonamide derivatives were investigated for their interaction with 12 mammalian alpha-carbonic anhydrases (CAs, EC 4.2.1.1), and three bacterial/archaeal CAs belonging to the alpha-, beta-, and gamma-CA class, respectively. X-ray crystal structure of the three inhibitors in complex with the dominant human isozyme CA II revealed a particular binding mode within the cavity. The sulfonamide group in meta-position to the Zn(2+)-coordinated SO(2)NH(2) moiety was oriented toward the hydrophilic side of the active site cleft, establishing hydrogen bonds with His64, Asn67, Gln92, and Thr200. The plane of the phenyl moiety of the inhibitors was rotated by 45 degrees and tilted by 10 degrees with respect to its most recurrent orientation in other CA II-sulfonamide complexes.
研究了三种苯-1,3-二磺酰胺衍生物与12种哺乳动物α-碳酸酐酶（CAs，EC 4.2.1.1）以及分别属于α-、β-和γ-CA类的三种细菌/古细菌CAs的相互作用。三种抑制剂与主要的人类同工酶CA II形成复合物的X射线晶体结构揭示了其在腔内的一种特殊结合模式。与Zn(2+)配位的SO(2)NH(2)部分处于间位的磺酰胺基团朝向活性位点裂隙的亲水侧，与His64、Asn67、Gln92和Thr200形成氢键。抑制剂苯部分的平面相对于其在其他CA II-磺酰胺复合物中最常见的取向旋转了45度并倾斜了10度。
