Sulphonamide inhibition profile of Staphylococcus aureus ß-carbonic anhydrase.
J Enzyme Inhib Med Chem
; 35(1): 1834-1839, 2020 Dec.
Article
en En
| MEDLINE
| ID: mdl-32972256
ABSTRACT
This paper presents the production and kinetic and inhibitory characterisation of ß-carbonic anhydrase from the opportunistic bacterium Staphylococcus aureus (SauBCA). From the eight different carbonic anhydrase (CA) families known to date, humans have only the α-form, whereas many clinically relevant pathogens have ß- and/or γ-form(s). Based on this discovery, ß- and γ-CAs have been introduced as promising new anti-infective targets. The results of this study revealed that recombinant SauBCA possesses significant CO2 hydration activity with a kcat of 1.46 × 105 s-1 and a kcat/KM of 2.56 × 107 s- 1M-1. Its enzymatic function was inhibited by various sulphonamides in the nanomolar - micromolar range, and the Ki of acetazolamide was 628 nM. The best inhibitor was the clinically used sulfamide agent famotidine (Ki of 71 nM). The least efficient inhibitors were zonisamide and dorzolamide. Our work encourages further investigations of SauBCA in an attempt to discover novel drugs against staphylococcal infections.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sulfonamidas
/
Inhibidores de Anhidrasa Carbónica
/
Anhidrasas Carbónicas
/
Antiinfecciosos
Límite:
Humans
Idioma:
En
Revista:
J Enzyme Inhib Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Finlandia