Three benzene-1,3-disulfonamide derivatives were investigated for their interaction with 12 mammalian a-carbonic anhydrases (CAs, EC 4.2.1.1), and three bacterial/archaeal CAs belonging to the ?-, ?-, and ?-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 Zn2+-coordinated SO2NH2 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° and tilted by 10° with respect to its most recurrent orientation in other CA II-sulfonamide complexes.
Carbonic anhydrase inhibitors: Inhibition of human, bacterial, and archaeal isozymes with benzene-1,3-disulfonamides - Solution and crystallographic studies
Alterio V;De Simone G;Monti SM;
2007
Abstract
Three benzene-1,3-disulfonamide derivatives were investigated for their interaction with 12 mammalian a-carbonic anhydrases (CAs, EC 4.2.1.1), and three bacterial/archaeal CAs belonging to the ?-, ?-, and ?-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 Zn2+-coordinated SO2NH2 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° and tilted by 10° with respect to its most recurrent orientation in other CA II-sulfonamide complexes.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
