Cloning, purification, kinetic and anion inhibition studies of a recombinant β-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salaris
Autor: | 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 |
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Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: | |
Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 37, Iss 1, Pp 1577-1586 (2022) |
Druh dokumentu: | article |
ISSN: | 14756366 1475-6374 1475-6366 |
DOI: | 10.1080/14756366.2022.2080818 |
Popis: | 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. |
Databáze: | Directory of Open Access Journals |
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