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.
Joseph
Pascale
P
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.
Turtaut
François
F
Ouahrani-Bettache
Safia
S
Montero
Jean-Louis
JL
Nishimori
Isao
I
Minakuchi
Tomoko
T
Vullo
Daniela
D
Scozzafava
Andrea
A
Köhler
Stephan
S
Winum
Jean-Yves
JY
Supuran
Claudiu T
CT
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