Kinetic characterization and quaternary structure of glutamate racemase from the periodontal anaerobe Fusobacterium nucleatum

Arch Biochem Biophys. 2009 Nov;491(1-2):16-24. doi: 10.1016/j.abb.2009.09.009. Epub 2009 Sep 20.

Abstract

Cofactor-independent glutamate racemases (GRs) that supply the d-glutamate required for biosynthesis of the peptidoglycan that encapsulates bacterial cells are attractive targets for the development of antibacterial drugs. Recombinant GR from Fusobacterium nucleatum (FnGR), a Gram-negative anaerobe involved in periodontal disease, was overproduced, purified, and characterized. Unlike most other GRs, FnGR is a pseudosymmetric enzyme, catalyzing the racemization of glutamate enantiomers with similar kinetic parameters (k(cat)(L-->D)=17.4+/-0.8s(-1), K(m)(L-->D)=1.04+/-0.07mM, k(cat)(D-->L)=26+/-1s(-1), and K(m)(D-->L)=1.7+/-0.1mM; [corrected] pH optimum approximately 8.5). Mutational analysis of residue 151 (A151V) located at the entryway to the active site revealed that FnGR is very sensitive to increased steric bulk at this position. Blue native-polyacrylamide gel electrophoresis, Ferguson plot analyses, and cross-linking studies, indicated that FnGR existed predominately as dimers. Unlike Bacillus subtilis GR, the presence of glutamate did not significantly alter the position of the monomer-dimer equilibrium of FnGR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / metabolism
  • Amino Acid Isomerases / chemistry*
  • Amino Acid Isomerases / genetics
  • Amino Acid Isomerases / isolation & purification
  • Amino Acid Isomerases / metabolism*
  • Amino Acid Sequence
  • Biocatalysis
  • Biofilms
  • Cloning, Molecular
  • Drug Discovery
  • Fusobacterium nucleatum / enzymology*
  • Fusobacterium nucleatum / physiology
  • Hydrogen-Ion Concentration
  • Kinetics
  • Molecular Sequence Data
  • Open Reading Frames / genetics
  • Periodontal Diseases / microbiology
  • Protein Structure, Quaternary*
  • Substrate Specificity

Substances

  • Amino Acid Isomerases
  • glutamate racemase
  • Alanine