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

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, CO(2) + H(2)O ⇋ HCO(3)(−) + H(+) with a k(cat) of...

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Bibliographic Details
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.
Format: Text
Language:English
Published: Taylor & Francis 2022
Subjects:
Original Article
Atlantic salmon
Online Access:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176631/
http://www.ncbi.nlm.nih.gov/pubmed/35637617
https://doi.org/10.1080/14756366.2022.2080818
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Summary: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, CO(2) + H(2)O ⇋ HCO(3)(−) + H(+) with a k(cat) of 1.1 × 10(5) s(−1) and a k(cat)/K(m) of 7.58 × 10(6) M(−1) × s(−1). This activity was inhibited by acetazolamide (K(I) 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 (K(I) of 81 µM), N,N-diethyldithiocarbamate (K(I) of 67 µM) and sulphamic acid (K(I) 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.

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