biostudies-literatureSippel KHNIGMS NIH HHS2898-2902https://www.ebi.ac.uk/biostudies/studies/S-EPMC2957018biostudies-literatureUnknown1(19)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.The journal of physical chemistry lettersSynchrotron Radiation Provides a Plausible Explanation for the Generation of a Free Radical Adduct of Thioxolone in Mutant Carbonic Anhydrase II.PMC2957018R01 GM025154-33R01 GM025154Sippel KHAgbandje-McKenna MKiddle JJTripp BCMcKenna RGenis CGovindasamy LfalseSynchrotron Radiation Provides a Plausible Explanation for the Generation of a Free Radical Adduct of Thioxolone in Mutant Carbonic Anhydrase II.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.2010-01-01T00:00:00Z2010 Oct2020-11-19T14:27:52Z2019-03-27T00:34:58ZS-EPMC29570182097612210.1021/jz100954h