Cloning, characterization, and inhibition studies of a beta-carbonic anhydrase from Brucella suis.
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.
Centre d'Etudes d'Agents Pathogenes et Biotechnologies pour la Sante, UMR 5236 CNRS-UM1-UM2, Universite Montpellier II, cc100, Place E Bataillon, 34095 Montpellier, France.
Pascale
P
Joseph
François
F
Turtaut
Safia
S
Ouahrani-Bettache
Jean-Louis
JL
Montero
Isao
I
Nishimori
Tomoko
T
Minakuchi
Daniela
D
Vullo
Andrea
A
Scozzafava
Stephan
S
Köhler
Jean-Yves
JY
Winum
Claudiu T
CT
Supuran
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D041021:Brucella suis / Q000201:enzymology* / Q000235:genetics; D002006:Brucellosis / Q000188:drug therapy*; D002256:Carbonic Anhydrases / Q000187:drug effects / Q000235:genetics*; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology*
D004269:DNA, Bacterial; D013449:Sulfonamides; D002256:Carbonic Anhydrases