Sulfonamide inhibition studies of the gamma-carbonic anhydrase from the Antarctic bacterium Pseudoalteromonas haloplanktis

The Antarctic bacterium Pseudoalteromonas haloplanktis encodes for a gamma-class carbonic anhydrase (CA, EC 4.2.1.1), which was cloned, purified and characterized. The enzyme (PhaCA gamma) has a good catalytic activity for the physiologic reaction of CO2 hydration to bicarbonate and protons, with a k(cat) of 1.4 x 10(5) s(-1) and a k(cat)/K-m of 1.9 x 10(6) M-1 x s(-1). A series of sulfonamides and a sulfamate were investigated as inhibitors of the new enzyme. Methazolamide and indisulam showed the best inhibitory properties (K(I)s of 86.7-94.7 nM). This contribution shed new light on gamma-CAs inhibition profiles with a relevant class of pharmacologic agents. (C) 2015 Elsevier Ltd. All rights reserved.