Abstract
We report the first activation study of the β-class carbonic anhydrase (CA, EC 4.2.1.1) encoded in the genome of the protozoan pathogen Trichomonas vaginalis, TvaCA1. Among 24 amino acid and amine activators investigated, derivatives incorporating a second carboxylic moiety, such as L-Asp, L- and D-Glu, were devoid of activating effects up to concentrations of 50 µM within the assay system, whereas the corresponding compounds with a CONH2 moiety, i.e. L-Gln and L-Asn showed modest activating effects, with activation constants in the range of 26.9 − 32.5 µM. Moderate activation was observed with L- and D-DOPA, histamine, dopamine, serotonin, (2-Aminoethyl)pyridine/piperazine and morpholine (KA‘s ranging between 8.3 and 14.5 µM), while the best activators were L-and D-Trp, L-and D-Tyr and 4-amino-Phe, which showed KA‘s ranging between 3.0 and 5.1 µM. Understanding in detail the activation mechanism of β-CAs may be relevant for the design of enzyme activity modulators with potential clinical significance.
Original language | English |
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Pages (from-to) | 758-763 |
Number of pages | 6 |
Journal | JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY |
Volume | 36 |
Issue number | 1 |
DOIs | |
Publication status | Published - Mar 2021 |
Publication type | A1 Journal article-refereed |
Keywords
- activator
- Amine
- amino acid
- carbonic anhydrase
- Trichomonas vaginalis
Publication forum classification
- Publication forum level 1
ASJC Scopus subject areas
- Pharmacology
- Drug Discovery