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?-Carbonic Anhydrases Possess Thioesterase Activity.

ABSTRACT: The ?-carbonic anhydrases (CAs, EC 4.2.1.1) show catalytic versatility acting as esterases with carboxylic, sulfonic, and phosphate esters. Here we prove by kinetic, spectroscopic, and MS studies that they also possess thioesterase activity with a dithiocarbamate ester as a substrate (PhSO2NHCSSMe). Its CA-mediated hydrolysis leads to benzenesulfonamide, methyl mercaptan, and COS. The CA thioesterase activity may be useful for designing prodrug enzyme inhibitors, whereas some CA isoforms may use this activity for modulating physiologic/pathologic processes, which are possibly amenable to drug discovery of agents with multiple mechanisms of action.

SUBMITTER: Tanc M

PROVIDER: S-EPMC4360143 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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α-Carbonic Anhydrases Possess Thioesterase Activity.

Tanc Muhammet M Carta Fabrizio F Scozzafava Andrea A Supuran Claudiu T CT

ACS medicinal chemistry letters 20150119 3

The α-carbonic anhydrases (CAs, EC 4.2.1.1) show catalytic versatility acting as esterases with carboxylic, sulfonic, and phosphate esters. Here we prove by kinetic, spectroscopic, and MS studies that they also possess thioesterase activity with a dithiocarbamate ester as a substrate (PhSO2NHCSSMe). Its CA-mediated hydrolysis leads to benzenesulfonamide, methyl mercaptan, and COS. The CA thioesterase activity may be useful for designing prodrug enzyme inhibitors, whereas some CA isoforms may use ...[more]

PMID: 25815148

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