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Cloning, characterization, and inhibition studies of a beta-carbonic anhydrase from Brucella suis.

Journal of medicinal chemistry (2010-02-18)
Pascale Joseph, François Turtaut, Safia Ouahrani-Bettache, Jean-Louis Montero, Isao Nishimori, Tomoko Minakuchi, Daniela Vullo, Andrea Scozzafava, Stephan Köhler, Jean-Yves Winum, Claudiu T Supuran
ABSTRACT

A beta-carbonic anhydrase (CA, EC 4.2.1.1) from the bacterial pathogen Brucella suis, bsCA 1, has been cloned, purified, and characterized kinetically. bsCA 1 has appreciable activity as catalyst for the hydration of CO(2) to bicarbonate, with a k(cat) of 6.4 x 10(5) s(-1) and k(cat)/K(m) of 3.9 x 10(7) M(-1).s(-1). A panel of 38 sulfonamides and one sulfamate have been investigated for inhibition of this new beta-CA. All types of activities have been detected, with K(I)s in the range of 17 nM to 5.87 microM. The best bsCA 1 inhibitors were ethoxzolamide (17 nM), celecoxib (18 nM), dorzolamide (21 nM), valdecoxib, and sulpiride (19 nM). Whether bsCA 1 inhibitors may have application in the fight against brucellosis, an endemic disease and the major bacterial zoonosis, producing debilitating infection in humans and animals, warrants further studies.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sulfanilamide, ≥98%
Sigma-Aldrich
p-Toluenesulfonamide, ReagentPlus®, ≥99%
Sigma-Aldrich
Sulfanilamide, puriss. p.a., ≥99% (calc. to the dried substance)
Sigma-Aldrich
4-Sulfamoylbenzoic acid, 97%
Supelco
Sulfanilamide, VETRANAL®, analytical standard
Sigma-Aldrich
p-Toluenesulfonamide, reagent grade, 98%
Sigma-Aldrich
(±)-Sulpiride