Carbonic anhydrase activators: activation of the beta-carbonic anhydrase Nce103 from the yeast Saccharomyces cerevisiae with amines and amino acids

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1662-5. doi: 10.1016/j.bmcl.2009.01.105. Epub 2009 Feb 5.

Abstract

The protein encoded by the Nce103 gene of Saccharomyces cerevisiae, a beta-carbonic anhydrase (CA, EC 4.2.1.1) designated as scCA, was investigated for its activation with amines and amino acids. scCA was poorly activated by amino acids such as l-/d-His, Phe, DOPA, Trp (K(A)s of 82-90 microM) and more effectively activated by amines such as histamine, dopamine, serotonin, pyridyl-alkylamines, aminoethyl-piperazine/morpholine (K(A)s of 10.2-21.3 microM). The best activator was l-adrenaline, with an activation constant of 0.95 microM. This study may help to better understand the catalytic/activation mechanisms of the beta-CAs and eventually to design modulators of CA activity for similar enzymes present in pathogenic fungi, such as Candida albicans and Cryptococcus neoformans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Candida albicans / metabolism
  • Carbonic Anhydrases / metabolism*
  • Catalysis
  • Catalytic Domain
  • Cryptococcus neoformans / enzymology
  • Drug Design
  • Enzyme Activation
  • Epinephrine / chemistry
  • Humans
  • Kinetics
  • Models, Chemical
  • Protein Isoforms
  • Saccharomyces cerevisiae / enzymology*
  • Tryptophan / chemistry

Substances

  • Amino Acids
  • Protein Isoforms
  • Tryptophan
  • Carbonic Anhydrases
  • Epinephrine