Bioorganic & Medicinal Chemistry Letters 2010-03-01

Carbonic anhydrase activators: Activation of the beta-carbonic anhydrase from the pathogenic yeast Candida glabrata with amines and amino acids.

Alessio Innocenti, Worraanong Leewattanapasuk, Gheorghe Manole, Andrea Scozzafava, Fritz A Mühlschlegel, Claudiu T Supuran

Index: Bioorg. Med. Chem. Lett. 20 , 1701-4, (2010)

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Abstract

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.Copyright 2010 Elsevier Ltd. All rights reserved.