Carbonic anhydrase activators: Activation of the beta-carbonic anhydrase from the pathogenic yeast Candida glabrata with amines and amino acids.
The protein encoded by the NCE103 gene of Candida glabrata, a beta-carbonic anhydrase (CA, EC 4.2.1.1) designated as CgCA, was investigated for its activation with amines and amino acids. CgCA was weakly activated by amino acids such as l-/d-His, l-Phe, l-DOPA, and l-Trp and by histamine or dopamine (K(A)s of 21.2-37microM) but more effectively activated by d-Phe, d-DOPA, d-Trp as well as serotonin, pyridyl-alkylamines, aminoethyl-piperazine/morpholine (K(A)s of 10.1-16.7microM). The best activators were l-/d-Tyr, with activation constants of 7.1-9.5microM. This study may bring a better understanding of the catalytic/activation mechanisms of beta-CAs from pathogenic fungi.
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
Alessio
A
Innocenti
Worraanong
W
Leewattanapasuk
Gheorghe
G
Manole
Andrea
A
Scozzafava
Fritz A
FA
Mühlschlegel
Claudiu T
CT
Supuran
D000588:Amines / Q000737:chemistry* / Q000494:pharmacology; D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology; D041221:Candida glabrata / Q000201:enzymology*; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship
D000588:Amines; D000596:Amino Acids; D011994:Recombinant Proteins; D002256:Carbonic Anhydrases