同步辐射为突变型碳酸酐酶II中硫氧杂环戊酮自由基加合物的产生提供了一个合理的解释。
Synchrotron Radiation Provides a Plausible Explanation for the Generation of a Free Radical Adduct of Thioxolone in Mutant Carbonic Anhydrase II.
作者信息
Sippel Katherine H, Genis Caroli, Govindasamy Lakshmanan, Agbandje-McKenna Mavis, Kiddle James J, Tripp Brian C, McKenna Robert
机构信息
Department of Biochemistry and Molecular Biology, P.O. Box 100245, College of Medicine, University of Florida, Gainesville, Florida 32610.
出版信息
J Phys Chem Lett. 2010 Oct 7;1(19):2898-2902. doi: 10.1021/jz100954h.
Thioxolone acts as a prodrug in the presence of carbonic anhydrase II (CA II), whereby the molecule is cleaved by thioester hydrolysis to the carbonic anhydrase inhibitor, 4-mercaptobenzene-1,3-diol (TH0). Thioxolone was soaked into the proton transfer mutant H64A of CA II in an effort to capture a reaction intermediate via X-ray crystallography. Structure determination of the 1.2 Å resolution data revealed the TH0 had been modified to a 4,4'-disulfanediyldibenzene-1,3-diol, a product of crystallization conditions, and a zinc ligated 2,4-dihydroxybenzenesulfenic acid, most likely induced by radiation damage. Neither ligand was likely a result of an enzymatic mechanism.
在碳酸酐酶II（CA II）存在的情况下，噻唑olone作为前药起作用，分子通过硫酯水解裂解为碳酸酐酶抑制剂4-巯基苯-1,3-二醇（TH0）。将噻唑olone浸泡到CA II的质子转移突变体H64A中，试图通过X射线晶体学捕获反应中间体。1.2 Å分辨率数据的结构测定表明，TH0已被修饰为4,4'-二硫烷基二苯-1,3-二醇，这是结晶条件的产物，以及一种锌连接的2,4-二羟基苯亚磺酸，很可能是由辐射损伤引起的。这两种配体都不太可能是酶促机制的结果。
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