Cloning, purification, kinetic and anion inhibition studies of a recombinant β-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salaris. (31st December 2022)

• Record Type: Journal Article
• Authors: Aspatwar, Ashok; Barker, Harlan; Aisala, Heidi; Zueva, Ksenia; Kuuslahti, Marianne; Tolvanen, Martti; Primmer, Craig R.; Lumme, Jaakko; Bonardi, Alessandro; Tripathi, Amit; Parkkila, Seppo; Supuran, Claudiu T.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 37:Number 1(2022)
• Page Start: 1577
• Page End: 1586
• Publication Date: 2022-12-31
• Subjects: Carbonic anhydrase -- Gyrodactylus salaris -- kinetics -- anion inhibitors -- sulphamic acid; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2022.2080818
• Languages: English
• ISSNs: 1475-6366

Abstract

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 + H2 O ⇋ HCO3 − + H + with a kcat of 1.1 × 10 5 s −1 and a kcat /Km of 7.58 × 10 6 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.