Innocenti, Alessio and Hall, Rebecca A. and Scozzafava, Andrea and Mühlschlegel, Fritz A. and Supuran, Claudiu T. (2010) Carbonic anhydrase activators: activation of the beta-carbonic anhydrases from the pathogenic fungi Candida albicans and Cryptococcus neoformans with amines and amino acids. Bioorganic & Medicinal Chemistry, 18 (3). pp. 1034-1037. ISSN 0968-0896. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)
The proteins encoded by the Nce103 genes of Candida albicans and Cryptococcus neoformans are catalytically active beta-carbonic anhydrases (CAs, EC 22.214.171.124) playing various roles in the life cycle of these fungal pathogens, such as CO(2) sensing, regulation of capsule biosynthesis, filamentation, and adaptation of the organism to various pH and CO(2) 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 microM. More effective activators were some amines such as histamine, dopamine, 2-aminoethyl-piperazine, and L-adrenaline (K(A)s of 13.2-18.5 microM). The best CaNce103 activators were L- and D-Dopa, with K(A)s of 0.96-2.5 microM. 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 microM. 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.
|Divisions:||Faculties > Science Technology and Medical Studies > School of Biosciences > Biomedical Research Group|
|Depositing User:||Sue Davies|
|Date Deposited:||29 Jun 2011 16:35|
|Last Modified:||22 Apr 2014 14:38|
|Resource URI:||https://kar.kent.ac.uk/id/eprint/27486 (The current URI for this page, for reference purposes)|