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

• Published in: Journal of Enzyme Inhibition and Medicinal Chemistry
• Main 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.
• Other Authors: Tampere University, BioMediTech, Clinical Medicine, Department of Clinical Chemistry
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2022
• Subjects: 3111 Biomedicine; Atlantic salmon
• Online Access: https://trepo.tuni.fi/handle/10024/141798; https://doi.org/10.1080/14756366.2022.2080818

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. Peer reviewed