Sulphonamide inhibition profile of Staphylococcus aureus β-carbonic anhydrase

Linda J. Urbanski, Silvia Bua, Andrea Angeli, Marianne Kuuslahti, Vesa P. Hytönen, Claudiu T. Supuran, Seppo Parkkila

Research output: Contribution to journalArticleScientificpeer-review

2 Citations (Scopus)
5 Downloads (Pure)

Abstract

This paper presents the production and kinetic and inhibitory characterisation of β-carbonic anhydrase from the opportunistic bacterium Staphylococcus aureus (SauBCA). From the eight different carbonic anhydrase (CA) families known to date, humans have only the α-form, whereas many clinically relevant pathogens have β- and/or γ-form(s). Based on this discovery, β- and γ-CAs have been introduced as promising new anti-infective targets. The results of this study revealed that recombinant SauBCA possesses significant CO2 hydration activity with a kcat of 1.46 × 105 s−1 and a kcat/KM of 2.56 × 107 s− 1M−1. Its enzymatic function was inhibited by various sulphonamides in the nanomolar − micromolar range, and the Ki of acetazolamide was 628 nM. The best inhibitor was the clinically used sulfamide agent famotidine (Ki of 71 nM). The least efficient inhibitors were zonisamide and dorzolamide. Our work encourages further investigations of SauBCA in an attempt to discover novel drugs against staphylococcal infections.

Original languageEnglish
Pages (from-to)1834-1839
Number of pages6
JournalJOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
Volume35
Issue number1
DOIs
Publication statusPublished - 2020
Publication typeA1 Journal article-refereed

Keywords

  • inhibition
  • kinetics
  • Staphylococcus aureus
  • sulphonamides
  • β-carbonic anhydrase

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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