The delta-carbonic anhydrase (CA, EC 4.2.1.1) TweCA from the marine diatom Thalassiosira weissflogii has recently been cloned, purified and its activity/inhibition with anions investigated. Here we report the first sulfonamide/sulfamate inhibition study of a delta-class CA. Among the 40 such compounds investigated so far, 3-bromosulfanilamide, acetazolamide, ethoxzolamide, dorzolamide and brinzolamide were the most effective TweCA inhibitors detected, with K(I)s of 49.6-118 nM. Many simple aromatic sulfonamides as well as dichlorophenamide, benzolamide, topiramate, zonisamide, indisulam and valdecoxib were medium potency inhibitors, (K(I)s of 375-897 nM). Saccharin and hydrochlorothiazide were ineffective inhibitors of the delta-class enzyme, with K(I)s of 4.27-9.20 mu M. The inhibition profile of the delta-CA is very different from that of alpha-, beta- and gamma-CAs from different organisms. Although no X-ray crystal structure of this enzyme is available, we hypothesize that as for other CA classes, the sulfonamides inhibit the enzymatic activity by binding to the Zn(II) ion from the delta-CA active site. (C) 2013 Elsevier Ltd. All rights reserved.
