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. 2016 Dec;590(23):4414-4428.
doi: 10.1002/1873-3468.12462. Epub 2016 Nov 7.

Structure and Inhibition of N-acetylneuraminate Lyase From Methicillin-Resistant Staphylococcus Aureus

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Structure and Inhibition of N-acetylneuraminate Lyase From Methicillin-Resistant Staphylococcus Aureus

Rachel A North et al. FEBS Lett. .
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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.

Keywords: N-acetylneuraminate lyase; antibiotic resistance; drug discovery; inhibitor; methicillin-resistant Staphylococcus aureus; sialic acid degradation; structure.

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