Journal
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
Volume 35, Issue 1, Pages 1545-1554Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2020.1800670
Keywords
Carbonic anhydrase; sulphonamides; inhibitors; antibacterials; Escherichia coli
Ask authors/readers for more resources
Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous metalloenzymes involved in biosynthetic processes, transport, supply, and balance of CO2/HCO(3)(-)into the cell. In Bacteria, CAs avoid the depletion of the dissolved CO2/HCO(3)(-)from the cell, providing them to the central metabolism that is compromised without the CA activity. The involvement of CAs in the survival, pathogenicity, and virulence of several bacterial pathogenic species is recent. Here, we report the kinetic properties of the recombinant gamma-CA (EcoCA gamma) encoded in the genome ofEscherichia coli. EcoCA gamma is an excellent catalyst for the physiological CO(2)hydration reaction to bicarbonate and protons, with a k(cat)of 5.7 x 10(5) s(-1)and k(cat)/K(M)of 6.9 x 10(6) M(-1)s(-1). The EcoCA gamma inhibition profile with a broad series of known CA inhibitors, the substituted benzene-sulphonamides, and clinically licenced drugs was explored. Benzolamide showed a K(I)lower than 100 nM. Our study reinforces the hypothesis that the synthesis of new drugs capable of interfering selectively with the bacterial CA activity, avoiding the inhibition of the human alpha-CAs, is achievable and may lead to novel antibacterials.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available