Sulfonamide inhibition studies of the γ-carbonic anhydrase from the Antarctic bacterium Pseudoalteromonas haloplanktis

Bioorg Med Chem Lett. 2015 Sep 1;25(17):3550-5. doi: 10.1016/j.bmcl.2015.06.079. Epub 2015 Jul 3.

Abstract

The Antarctic bacterium Pseudoalteromonas haloplanktis encodes for a γ-class carbonic anhydrase (CA, EC 4.2.1.1), which was cloned, purified and characterized. The enzyme (PhaCAγ) has a good catalytic activity for the physiologic reaction of CO2 hydration to bicarbonate and protons, with a k(cat) of 1.4×10(5) s(-1) and a k(cat)/K(m) of 1.9×10(6) M(-1)×s(-1). A series of sulfonamides and a sulfamate were investigated as inhibitors of the new enzyme. Methazolamide and indisulam showed the best inhibitory properties (K(I)s of 86.7-94.7 nM). This contribution shed new light on γ-CAs inhibition profiles with a relevant class of pharmacologic agents.

Keywords: Antarctic carbonic anhydrase; Carbonic anhydrase; Cold adaptation; Cold enzymes; Hydratase activity; Inhibitors; Metalloenzymes; Psychrophiles; Sulfonamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acclimatization
  • Amino Acid Sequence
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / chemistry
  • Carbonic Anhydrases / genetics
  • Carbonic Anhydrases / metabolism*
  • Cold Temperature
  • Humans
  • Molecular Sequence Data
  • Phylogeny
  • Pseudoalteromonas / drug effects
  • Pseudoalteromonas / enzymology*
  • Pseudoalteromonas / genetics
  • Sequence Alignment
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology*

Substances

  • Carbonic Anhydrase Inhibitors
  • Sulfonamides
  • Carbonic Anhydrases