Sulfonamide inhibition studies of the γ-carbonic anhydrase from the Antarctic cyanobacterium Nostoc commune

Bioorg Med Chem. 2015 Apr 15;23(8):1728-34. doi: 10.1016/j.bmc.2015.02.045. Epub 2015 Mar 4.

Abstract

A carbonic anhydrase (CA, EC 4.2.1.1) belonging to the γ-class has been cloned, purified and characterized from the Antarctic cyanobacterium Nostoc commune. The enzyme showed a good catalytic activity for the physiologic reaction (hydration of carbon dioxide to bicarbonate and a proton) with the following kinetic parameters, kcat of 9.5×10(5)s(-1) and kcat/KM of 8.3×10(7)M(-1)s(-1), being the γ-CA with the highest catalytic activity described so far. A range of aromatic/heterocyclic sulfonamides and one sulfamate were investigated as inhibitors of the new enzyme, denominated here NcoCA. The best NcoCA inhibitors were some sulfonylated sulfanilamide derivatives possessing elongated molecules, aminobenzolamide, acetazolamide, benzolamide, dorzolamide, brinzolamide and topiramate, which showed inhibition constants in the range of 40.3-92.3nM. As 1,5-bisphosphate carboxylase/oxygenase (RubisCO) and γ-CAs are closely associated in carboxysomes of cyanobacteria for enhancing the affinity of RubisCO for CO2 and the efficiency of photosynthesis, investigation of this new enzyme and its affinity for modulators of its activity may bring new insights in these crucial processes.

Keywords: Antarctic carbonic anhydrase; Carbonic anhydrase; Cyanobacteria; Hydratase activity; Metalloenzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / chemistry
  • Carbonic Anhydrases / metabolism
  • Molecular Sequence Data
  • Nostoc commune / chemistry
  • Nostoc commune / drug effects*
  • Nostoc commune / enzymology*
  • Sequence Alignment
  • Sulfanilamide
  • Sulfanilamides / chemistry
  • Sulfanilamides / pharmacology
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology*
  • Thiazines / chemistry
  • Thiazines / pharmacology
  • Thiophenes / chemistry
  • Thiophenes / pharmacology

Substances

  • Carbonic Anhydrase Inhibitors
  • Sulfanilamides
  • Sulfonamides
  • Thiazines
  • Thiophenes
  • Sulfanilamide
  • brinzolamide
  • dorzolamide
  • Carbonic Anhydrases