Unexpected N-acetylation of capreomycin by mycobacterial Eis enzymes.
J Antimicrob Chemother
; 68(4): 800-5, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23233486
ABSTRACT
OBJECTIVES:
The enhanced intracellular survival (Eis) protein from Mycobacterium tuberculosis (Eis_Mtb), a regio-versatile N-acetyltransferase active towards many aminoglycosides (AGs), confers resistance to kanamycin A in some cases of extensively drug-resistant tuberculosis (XDR-TB). We assessed the activity of Eis_Mtb and of its homologue from Mycobacterium smegmatis (Eis_Msm) against a panel of anti-tuberculosis (TB) drugs and lysine-containing compounds. METHODS ANDRESULTS:
Both enzymes acetylated capreomycin and some lysine-containing compounds, but not other non-AG non-lysine-containing drugs tested. Modelling studies predicted the site of modification on capreomycin to be one of the two primary amines in its ß-lysine side chain. Using Eis_Mtb, we established via nuclear magnetic resonance (NMR) spectroscopy that acetylation of capreomycin occurs on the ε-amine of the ß-lysine side chain. Using Msm, we also demonstrated for the first time to our knowledge that acetylation of capreomycin results in deactivation of the drug.CONCLUSIONS:
Eis is a unique acetyltransferase capable of inactivating the anti-TB drug capreomycin, AGs and other lysine-containing compounds.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Capreomicina
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Mycobacterium smegmatis
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Mycobacterium tuberculosis
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Antígenos de Bactérias
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Antituberculosos
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article