Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
Bioorg Med Chem Lett. 2010 Jan 15;20(2):474-8. doi: 10.1016/j.bmcl.2009.11.124. Epub 2009 Nov 27.
Trithiocarbonate (CS32-) inhibits with low micromolar affinities several mammalian carbonic anhydrases, CAs, EC 4.2.1.1 [Innocenti et al., Bioorg. Med. Chem. Lett. 2009, 19, 1855]. Here we report the X-ray crystal structure of the hCA II-trithiocarbonate adduct. Trithiocarbonate is monodentately bound to the Zn(II) ion and makes several hydrogen bonds with Thr199 and two water molecules from the enzyme active site. Its binding is different from that of ureate, another small inhibitor isosteric with trithiocarbonate but somehow mimicks the binding of the SO(2)NH moiety present in the sulfonamide inhibitors and is similar to that of bicarbonate. Compounds incorporating this new zinc-binding group, CS2-, may thus lead to new classes of potent inhibitors.
三硫代碳酸根（CS32-）以低微摩尔亲和力抑制几种哺乳动物碳酸酐酶，CA，EC 4.2.1.1 [Innocenti 等人，生物有机与医药化学快报。2009，19，1855]。在这里，我们报告了 hCA II-三硫代碳酸酯加合物的 X 射线晶体结构。三硫代碳酸根以单齿配位的方式与 Zn(II) 离子结合，并与 Thr199 和来自酶活性位点的两个水分子形成氢键。它的结合方式与脲不同，脲是三硫代碳酸酯的等排体小分子抑制剂，但在某种程度上模拟了磺酰胺抑制剂中存在的 SO(2)NH 部分的结合方式，与碳酸氢根相似。因此，包含这种新的锌结合基团 CS2-的化合物可能会导致新的强效抑制剂类别。
