Structure and inhibition of N-acetylneuraminate lyase from methicillin-resistant Staphylococcus aureus.
FEBS Lett
; 590(23): 4414-4428, 2016 Dec.
Article
en En
| MEDLINE
| ID: mdl-27943302
ABSTRACT
N-Acetylneuraminate lyase is the first committed enzyme in the degradation of sialic acid by bacterial pathogens. In this study, we analyzed the kinetic parameters of N-acetylneuraminate lyase from methicillin-resistant Staphylococcus aureus (MRSA). We determined that the enzyme has a relatively high KM of 3.2 mm, suggesting that flux through the catabolic pathway is likely to be controlled by this enzyme. Our data indicate that sialic acid alditol, a known inhibitor of N-acetylneuraminate lyase enzymes, is a stronger inhibitor of MRSA N-acetylneuraminate lyase than of Clostridium perfringens N-acetylneuraminate lyase. Our analysis of the crystal structure of ligand-free and 2R-sialic acid alditol-bound MRSA N-acetylneuraminate lyase suggests that subtle dynamic differences in solution and/or altered binding interactions within the active site may account for species-specific inhibition.
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Base de datos:
MEDLINE
Asunto principal:
Inhibidores Enzimáticos
/
Staphylococcus aureus Resistente a Meticilina
/
Oxo-Ácido-Liasas
Idioma:
En
Revista:
FEBS Lett
Año:
2016
Tipo del documento:
Article