Benzyl alcohol inhibits carbonic anhydrases by anchoring to the zinc coordinated water molecule

Biochem Biophys Res Commun. 2021 Apr 9:548:217-221. doi: 10.1016/j.bbrc.2021.02.067. Epub 2021 Feb 27.

Abstract

Up to date alcohols have been scarcely investigated as carbonic anhydrase (CA) inhibitors. To get more insights into the CA inhibition properties of this class of molecules, in this paper, by means of inhibition assays and X-ray crystallographic studies we report a detailed characterization of the CA inhibition properties and the binding mode to human CA II of benzyl alcohol. Results show that, although possessing a very simple scaffold, this molecule acts as a micromolar CA II inhibitor, which anchors to the enzyme active site by means of an H-bond interaction with the zinc bound solvent molecule. Taken together our results clearly indicate primary alcohols as a class of CA inhibitors that deserve to be more investigated.

Keywords: Benzyl alcohol; Carbonic anhydrase inhibition; Primary alcohol; Stopped flow CO(2) hydration assay; X-ray crystal structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetazolamide / pharmacology
  • Benzyl Alcohol / chemistry
  • Benzyl Alcohol / pharmacology*
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Catalytic Domain
  • Isoenzymes / metabolism
  • Models, Molecular
  • Water / metabolism*
  • Zinc / metabolism*

Substances

  • Carbonic Anhydrase Inhibitors
  • Isoenzymes
  • Water
  • Zinc
  • Benzyl Alcohol
  • Acetazolamide