Cloning, purification, kinetic and anion inhibition studies of a recombinant β-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salaris

Ashok Aspatwar, Harlan Barker, Heidi Aisala, Ksenia Zueva, Marianne Kuuslahti, Martti Tolvanen, Craig R. Primmer, Jaakko Lumme, Alessandro Bonardi, Amit Tripathi, Seppo Parkkila, Claudiu T. Supuran

Research output: Contribution to journalArticleScientificpeer-review

12 Citations (Scopus)
24 Downloads (Pure)

Abstract

A β-class carbonic anhydrase (CA, EC 4.2.1.1) was cloned from the genome of the Monogenean platyhelminth Gyrodactylus salaris, a parasite of Atlantic salmon. The new enzyme, GsaCAβ has a significant catalytic activity for the physiological reaction, CO2 + H2O ⇋ HCO3 + H+ with a kcat of 1.1 × 105 s−1 and a kcat/Km of 7.58 × 106 M−1 × s−1. This activity was inhibited by acetazolamide (KI of 0.46 µM), a sulphonamide in clinical use, as well as by selected inorganic anions and small molecules. Most tested anions inhibited GsaCAβ at millimolar concentrations, but sulfamide (KI of 81 µM), N,N-diethyldithiocarbamate (KI of 67 µM) and sulphamic acid (KI of 6.2 µM) showed a rather efficient inhibitory action. There are currently very few non-toxic agents effective in combating this parasite. GsaCAβ is subsequently proposed as a new drug target for which effective inhibitors can be designed.

Original languageEnglish
Pages (from-to)1577-1586
Number of pages10
JournalJOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
Volume37
Issue number1
DOIs
Publication statusPublished - 2022
Publication typeA1 Journal article-refereed

Keywords

  • anion inhibitors
  • Carbonic anhydrase
  • Gyrodactylus salaris
  • kinetics
  • sulphamic acid

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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