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, CO2 + H2O ⇋ HCO3− + H+ with a kcat of 1.1 × 105 s−...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2080818 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ashok Aspatwar |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T05:15:41Z |
| format | Article |
| id | doaj.art-bdf016d9e23e49eba9c8db7310530d47 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-04-14T05:15:41Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-bdf016d9e23e49eba9c8db7310530d472022-12-22T02:10:22ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013711577158610.1080/14756366.2022.2080818Cloning, purification, kinetic and anion inhibition studies of a recombinant β-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salarisAshok Aspatwar0Harlan Barker1Heidi Aisala2Ksenia Zueva3Marianne Kuuslahti4Martti Tolvanen5Craig R. Primmer6Jaakko Lumme7Alessandro Bonardi8Amit Tripathi9Seppo Parkkila10Claudiu T. Supuran11Faculty of Medicine and Health Technology, Tampere University, Tampere, FinlandFaculty of Medicine and Health Technology, Tampere University, Tampere, FinlandEcology and Genetics, University of Oulu, Oulu, FinlandDepartment of Biology, University of Turku, Turku, FinlandFaculty of Medicine and Health Technology, Tampere University, Tampere, FinlandDepartment of Computing, University of Turku, Turku, FinlandOrganismal and Evolutionary Biology Research Programme, University of Helsinki, Helsinki, FinlandEcology and Genetics, University of Oulu, Oulu, FinlandDepartment of Neuroscience, Psychology, Drug Research and Child’s Health, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Sesto Fiorentino, ItalyDepartment of Zoology, University of Lucknow, Lucknow, IndiaFaculty of Medicine and Health Technology, Tampere University, Tampere, FinlandDepartment of Neuroscience, Psychology, Drug Research and Child’s Health, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Sesto Fiorentino, ItalyA 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.https://www.tandfonline.com/doi/10.1080/14756366.2022.2080818Carbonic anhydraseGyrodactylus salariskineticsanion inhibitorssulphamic acid |
| spellingShingle | 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 Cloning, purification, kinetic and anion inhibition studies of a recombinant β-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salaris Journal of Enzyme Inhibition and Medicinal Chemistry Carbonic anhydrase Gyrodactylus salaris kinetics anion inhibitors sulphamic acid |
| title | Cloning, purification, kinetic and anion inhibition studies of a recombinant β-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salaris |
| title_full | Cloning, purification, kinetic and anion inhibition studies of a recombinant β-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salaris |
| title_fullStr | Cloning, purification, kinetic and anion inhibition studies of a recombinant β-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salaris |
| title_full_unstemmed | Cloning, purification, kinetic and anion inhibition studies of a recombinant β-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salaris |
| title_short | Cloning, purification, kinetic and anion inhibition studies of a recombinant β-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salaris |
| title_sort | cloning purification kinetic and anion inhibition studies of a recombinant β carbonic anhydrase from the atlantic salmon parasite platyhelminth gyrodactylus salaris |
| topic | Carbonic anhydrase Gyrodactylus salaris kinetics anion inhibitors sulphamic acid |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2080818 |
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