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. (2022)
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.
2022
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202208196555
https://urn.fi/URN:NBN:fi:tuni-202208196555
Kuvaus
Peer reviewed
Tiivistelmä
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.
Kokoelmat
- TUNICRIS-julkaisut [17001]