Cloning, purification, kinetic and anion inhibition studies of a recombinant beta-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: Helsinki Institute of Sustainability Science (HELSUS), Organismal and Evolutionary Biology Research Programme, Evolution, Conservation, and Genomics, Institute of Biotechnology, Biosciences, Helsinki Institute of Life Science HiLIFE
• Format: Article in Journal/Newspaper
• Language: English
• Published: Informa healthcare 2022
• Subjects: Carbonic anhydrase; Gyrodactylus salaris; kinetics; anion inhibitors; sulphamic acid; PATHOGENS CANDIDA-ALBICANS; CRYPTOCOCCUS-NEOFORMANS; SACCHAROMYCES-CEREVISIAE; CLASS ENZYMES; ISOZYME-II; ALPHA; IDENTIFICATION; ACTIVATION; SELECTION; ALIGNMENT; 1184 Genetics; developmental biology; physiology; Atlantic salmon
• Online Access: http://hdl.handle.net/10138/345315

A beta-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, GsaCA beta has a significant catalytic activity for the physiological reaction, CO2 + H2O (sic) HCO3- + H+ with a k(cat) of 1.1 x 10(5) s(-1) and a k(cat)/K-m of 7.58 x 10(6) M-1 x s(-1). This activity was inhibited by acetazolamide (K-I of 0.46 mu M), a sulphonamide in clinical use, as well as by selected inorganic anions and small molecules. Most tested anions inhibited GsaCA beta at millimolar concentrations, but sulfamide (K-I of 81 mu M), N,N-diethyldithiocarbamate (K-I of 67 mu M) and sulphamic acid (K-I of 6.2 mu M) showed a rather efficient inhibitory action. There are currently very few non-toxic agents effective in combating this parasite. GsaCA beta is subsequently proposed as a new drug target for which effective inhibitors can be designed. Peer reviewed