Carbonic anhydrase inhibitors. Cloning, characterization, and inhibition studies of a new beta-carbonic anhydrase from Mycobacterium tuberculosis.
The Rv3273 gene product of Mycobacterium tuberculosis, a beta-carbonic anhydrase (CA, EC 4.2.1.1), mtCA 3, shows appreciable catalytic activity for CO(2) hydration (k(cat) of 4.3 x 10(5) s(-1), and k(cat)/K(m) of 4.0 x 10(7) M(-1) x s(-1)). A series of sulfonamides/sulfamates was assayed for their interaction with mtCA 3. Sulfanilyl-sulfonamides, acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, benzolamide, and zonisamide, showed effective, submicromolar inhibition (K(I)s of 104-611 nM), the best inhibitor being 2-amino-pyrimidin-4-yl-sulfanilamide (K(I) of 91 nM).
Nishimori
Isao
I
Department of Gastroenterology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
Minakuchi
Tomoko
T
Vullo
Daniela
D
Scozzafava
Andrea
A
Innocenti
Alessio
A
Supuran
Claudiu T
CT