Escherichia coli γ-carbonic anhydrase: characterisation and effects of simple aromatic/heterocyclic sulphonamide inhibitors.
J Enzyme Inhib Med Chem
; 35(1): 1545-1554, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-32746656
ABSTRACT
Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous metalloenzymes involved in biosynthetic processes, transport, supply, and balance of CO2/HCO3 - into the cell. In Bacteria, CAs avoid the depletion of the dissolved CO2/HCO3 - 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 γ-CA (EcoCAγ) encoded in the genome of Escherichia coli. EcoCAγ is an excellent catalyst for the physiological CO2 hydration reaction to bicarbonate and protons, with a kcat of 5.7 × 105 s-1 and kcat/KM of 6.9 × 106 M-1 s-1. The EcoCAγ inhibition profile with a broad series of known CA inhibitors, the substituted benzene-sulphonamides, and clinically licenced drugs was explored. Benzolamide showed a KI 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 α -CAs, is achievable and may lead to novel antibacterials.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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Inibidores da Anidrase Carbônica
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Anidrases Carbônicas
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Escherichia coli
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article