Structure and inhibition of N ‐acetylneuraminate lyase from methicillin‐resistant Staphylococcus aureus

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 K M of 3.2 m m , 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 2 R ‐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.