Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176631/ https://www.ncbi.nlm.nih.gov/pubmed/35637617 http://dx.doi.org/10.1080/14756366.2022.2080818 |
_version_ | 1784722705644257280 |
---|---|
author | 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. |
author_facet | 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. |
author_sort | Aspatwar, Ashok |
collection | PubMed |
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, 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. |
format | Online Article Text |
id | pubmed-9176631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-91766312022-06-09 Cloning, purification, kinetic and anion inhibition studies of a recombinant β-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salaris 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. J Enzyme Inhib Med Chem Original Article 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. Taylor & Francis 2022-05-30 /pmc/articles/PMC9176631/ /pubmed/35637617 http://dx.doi.org/10.1080/14756366.2022.2080818 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article 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. Cloning, purification, kinetic and anion inhibition studies of a recombinant β-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salaris |
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 | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176631/ https://www.ncbi.nlm.nih.gov/pubmed/35637617 http://dx.doi.org/10.1080/14756366.2022.2080818 |
work_keys_str_mv | AT aspatwarashok cloningpurificationkineticandanioninhibitionstudiesofarecombinantbcarbonicanhydrasefromtheatlanticsalmonparasiteplatyhelminthgyrodactylussalaris AT barkerharlan cloningpurificationkineticandanioninhibitionstudiesofarecombinantbcarbonicanhydrasefromtheatlanticsalmonparasiteplatyhelminthgyrodactylussalaris AT aisalaheidi cloningpurificationkineticandanioninhibitionstudiesofarecombinantbcarbonicanhydrasefromtheatlanticsalmonparasiteplatyhelminthgyrodactylussalaris AT zuevaksenia cloningpurificationkineticandanioninhibitionstudiesofarecombinantbcarbonicanhydrasefromtheatlanticsalmonparasiteplatyhelminthgyrodactylussalaris AT kuuslahtimarianne cloningpurificationkineticandanioninhibitionstudiesofarecombinantbcarbonicanhydrasefromtheatlanticsalmonparasiteplatyhelminthgyrodactylussalaris AT tolvanenmartti cloningpurificationkineticandanioninhibitionstudiesofarecombinantbcarbonicanhydrasefromtheatlanticsalmonparasiteplatyhelminthgyrodactylussalaris AT primmercraigr cloningpurificationkineticandanioninhibitionstudiesofarecombinantbcarbonicanhydrasefromtheatlanticsalmonparasiteplatyhelminthgyrodactylussalaris AT lummejaakko cloningpurificationkineticandanioninhibitionstudiesofarecombinantbcarbonicanhydrasefromtheatlanticsalmonparasiteplatyhelminthgyrodactylussalaris AT bonardialessandro cloningpurificationkineticandanioninhibitionstudiesofarecombinantbcarbonicanhydrasefromtheatlanticsalmonparasiteplatyhelminthgyrodactylussalaris AT tripathiamit cloningpurificationkineticandanioninhibitionstudiesofarecombinantbcarbonicanhydrasefromtheatlanticsalmonparasiteplatyhelminthgyrodactylussalaris AT parkkilaseppo cloningpurificationkineticandanioninhibitionstudiesofarecombinantbcarbonicanhydrasefromtheatlanticsalmonparasiteplatyhelminthgyrodactylussalaris AT supuranclaudiut cloningpurificationkineticandanioninhibitionstudiesofarecombinantbcarbonicanhydrasefromtheatlanticsalmonparasiteplatyhelminthgyrodactylussalaris |