Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 18, Issue 3, Pages 1034-1037Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2009.12.058
Keywords
Carbonic anhydrase; beta-Class enzymes; Candida albicans; Cryptococcus neoformans; Amino acid; Amine; Enzyme-activator
Funding
- European Union
- MRC
- MRC [G0601049] Funding Source: UKRI
- Medical Research Council [G0601049] Funding Source: researchfish
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The proteins encoded by the Nce103 genes of Candida albicans and Cryptococcus neoformans are catalytically active beta-carbonic anhydrases (CAs, EC 4.2.1.1) playing various roles in the life cycle of these fungal pathogens, such as CO2 sensing, regulation of capsule biosynthesis, filamentation, and adaptation of the organism to various pH and CO2 conditions in various niches where the fungi grow. Here, we report the first activation study of these two enzymes, CaNce103 and Can2, respectively, with amines and amino acids. The C. albicans enzyme, CaNce103 was activated by amino acids such as L-/D-His, L-D-Trp, L-Tyr with K(A)s in the range of 19.5-46 mu M. More effective activators were some amines such as histamine, dopamine, 2-aminoethyl-piperazine, and L-adrenaline (K(A)s of 13.2-18.5 mu M). The best CaNce103 activators were L- and D-Dopa, with K(A)s of 0.96-2.5 mu M. The C. neoformans enzyme, Can2, showed much lower propensity to be activated by all these amino acids and amines, which had activation constants in the range of 28.7-47.2 mu M. The best Can2 activator was L-Trp. This study may help to better understand the catalytic/activation mechanisms of the beta-CAs and eventually to design CA activity modulators of such widespread enzymes in pathogenic fungi. (C) 2009 Elsevier Ltd. All rights reserved.
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