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

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


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.

Publication types

  • Letter

MeSH terms

  • Amino Acid Sequence
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Kinetics
  • Methicillin-Resistant Staphylococcus aureus / enzymology*
  • Models, Molecular
  • N-Acetylneuraminic Acid / metabolism
  • Oxo-Acid-Lyases / antagonists & inhibitors*
  • Oxo-Acid-Lyases / chemistry*
  • Oxo-Acid-Lyases / metabolism
  • Protein Structure, Quaternary
  • Species Specificity


  • Enzyme Inhibitors
  • Oxo-Acid-Lyases
  • N-acetylneuraminate lyase
  • N-Acetylneuraminic Acid