Carbonic anhydrase activators: activation of the beta-carbonic anhydrases from the pathogenic fungi Candida albicans and Cryptococcus neoformans with amines and amino acids

Alessio Innocenti, Rebecca Hall, Andrea Scozzafava, Fritz A Mühlschlegel, Claudiu T Supuran

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

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 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.
Original languageEnglish
Pages (from-to)1034-7
Number of pages4
JournalBioorganic & Medicinal Chemistry
Volume18
Issue number3
DOIs
Publication statusPublished - Feb 2010

Keywords

  • Amines
  • Amino Acids
  • Candida albicans
  • Carbonic Anhydrase I
  • Carbonic Anhydrases
  • Cryptococcus neoformans
  • Enzyme Activation
  • Structure-Activity Relationship

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