Anion inhibition studies of two new ß-carbonic anhydrases from the bacterial pathogen Legionella pneumophila.
Bioorg Med Chem Lett
; 24(4): 1127-32, 2014 Feb 15.
Article
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| MEDLINE
| ID: mdl-24461298
ABSTRACT
We investigated the cloning, catalytic activity and anion inhibition of the ß-class carbonic anhydrases (CAs, EC 4.2.1.1) from the bacterial pathogen Legionella pneumophila. Two such enzymes, lpCA1 and lpCA2, were found in the genome of this pathogen. These enzymes were determined to be efficient catalysts for CO2 hydration, with kcat values in the range of (3.4-8.3)×10(5) s(-1) and kcat/KM values of (4.7-8.5)×10(7) M(-1) s(-1). A set of inorganic anions and small molecules was investigated to identify inhibitors of these enzymes. Perchlorate and tetrafluoroborate were not acting as inhibitors (KI >200 mM), whereas sulfate was a very weak inhibitor for both lpCA1 and lpCA2 (KI values of 77.9-96.5 mM). The most potent lpCA1 inhibitors were cyanide, azide, hydrogen sulfide, diethyldithiocarbamate, sulfamate, sulfamide, phenylboronic acid and phenylarsonic acid, with KI values ranging from 6 to 94 µM. The most potent lpCA2 inhibitors were diethyldithiocarbamate, sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid, with KI values ranging from 2 to 13 µM. As these enzymes seem to be involved in regulation of phagosome pH during Legionella infection, inhibition of these targets may lead to antibacterial agents with a novel mechanism of action.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Legionella pneumophila
/
Anhidrasas Carbónicas
/
Inhibidores Enzimáticos
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Japón