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Structure and inhibition of N ‐acetylneuraminate lyase from methicillin‐resistant Staphylococcus aureus
Author(s) -
North Rachel A.,
Watson Andrew J. A.,
Pearce F. Grant,
MuscroftTaylor Andrew C.,
Friemann Rosmarie,
Fairbanks Antony J.,
Dobson Renwick C. J.
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12462
Subject(s) - lyase , enzyme , sialic acid , staphylococcus aureus , chemistry , microbiology and biotechnology , biochemistry , catabolism , ligand (biochemistry) , clostridium perfringens , bacteria , biology , receptor , genetics
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.