Structure and inhibition of N‐acetylneuraminate lyase from methicillin‐resistant Staphylococcus aureus
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 07, 2016
- Source ID
- 10.1002/1873-3468.12462
Entities
People
- Andrew C. Muscroft‐taylor
- Andrew J. A. Watson
- Antony J. Fairbanks
- F. Grant Pearce
- Rachel A North
- Renwick Dobson
- Rosmarie Friemann
Organizations
- Ministry of Business, Innovation and Employment
- Stanford University
- University of Canterbury
- University of Gothenburg
- University of Melbourne