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

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1701-4. doi: 10.1016/j.bmcl.2010.01.054. Epub 2010 Jan 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Amines / pharmacology
  • Amino Acids / chemistry*
  • Amino Acids / pharmacology
  • Candida glabrata / enzymology*
  • Carbonic Anhydrases / chemistry
  • Carbonic Anhydrases / genetics
  • Carbonic Anhydrases / metabolism*
  • Catalytic Domain
  • Enzyme Activation
  • Humans
  • Kinetics
  • Models, Molecular
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Structure-Activity Relationship

Substances

  • Amines
  • Amino Acids
  • Recombinant Proteins
  • Carbonic Anhydrases