Burkholderia pseudomallei γ-carbonic anhydrase is strongly activated by amino acids and amines

Bioorg Med Chem Lett. 2017 Jan 1;27(1):77-80. doi: 10.1016/j.bmcl.2016.11.027. Epub 2016 Nov 12.

Abstract

Activation of the γ-class carbonic anhydrase (CAs, EC 4.2.1.1) from the pathogenic bacterium Burkholderia pseudomallei (BpsγCA) with a series of natural and non-natural amino acids and aromatic/heterocyclic amines has been investigated. The best BpsγCA activators were d-His, l-DOPA, d-Trp, 4-amino-l-Phe, dopamine, 2-(2-aminoethyl)pyridine, 2-aminoethyl-piparazine/morpholine and l-adrenaline, which showed activation constants ranging between 9 and 86nM. The least effective activators were l-His, l-Phe and 2-pyridyl-methylamine, with KAs in the range of 1.73-24.7μM. As little is known about the role of γ-CAs in the lifecycle and virulence of this saprophytic bacterium, this study may shed some light on such phenomena. This is the first CA activation study of a γ-CA from a pathogenic bacterium, the only other such study being on the enzyme discovered in the archaeon Methanosarcina thermophila, Cam.

Keywords: Activator; Amine; Amino acid; Burkholderia pseudomallei; Carbonic anhydrase; Gamma-class enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Amines / pharmacology*
  • Amino Acids / chemistry
  • Amino Acids / pharmacology*
  • Burkholderia pseudomallei / enzymology*
  • Carbonic Anhydrases / metabolism*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Amines
  • Amino Acids
  • Carbonic Anhydrases