The Functional Unit of Neisseria meningitidis 3-Deoxy-ᴅ-Arabino-Heptulosonate 7-Phosphate Synthase Is Dimeric

PLoS One. 2016 Feb 1;11(2):e0145187. doi: 10.1371/journal.pone.0145187. eCollection 2016.

Abstract

Neisseria meningitidis 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (NmeDAH7PS) adopts a homotetrameric structure consisting of an extensive and a less extensive interface. Perturbation of the less extensive interface through a single mutation of a salt bridge (Arg126-Glu27) formed at the tetramer interface of all chains resulted in a dimeric DAH7PS in solution, as determined by small angle X-ray scattering, analytical ultracentrifugation and analytical size-exclusion chromatography. The dimeric NmeDAH7PSR126S variant was shown to be catalytically active in the aldol-like condensation reaction between D-erythrose 4-phosphate and phosphoenolpyruvate, and allosterically inhibited by L-phenylalanine to the same extent as the wild-type enzyme. The dimeric NmeDAH7PSR126S variant exhibited a slight reduction in thermal stability by differential scanning calorimetry experiments and a slow loss of activity over time compared to the wild-type enzyme. Although NmeDAH7PSR126S crystallised as a tetramer, like the wild-type enzyme, structural asymmetry at the less extensive interface was observed consistent with its destabilisation. The tetrameric association enabled by this Arg126-Glu27 salt-bridge appears to contribute solely to the stability of the protein, ultimately revealing that the functional unit of NmeDAH7PS is dimeric.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Deoxy-7-Phosphoheptulonate Synthase / chemistry
  • 3-Deoxy-7-Phosphoheptulonate Synthase / metabolism*
  • Biocatalysis
  • Chromatography, Gel
  • Conserved Sequence
  • Crystallography, X-Ray
  • Kinetics
  • Models, Molecular
  • Mutation / genetics
  • Neisseria meningitidis / enzymology*
  • Phenylalanine / pharmacology
  • Protein Multimerization*
  • Protein Structure, Quaternary
  • Scattering, Small Angle
  • Solutions
  • Time Factors

Substances

  • Solutions
  • Phenylalanine
  • 3-Deoxy-7-Phosphoheptulonate Synthase

Grants and funding

This work was funded by the New Zealand Marsden fund (UoC1105). This work was also supported by the New Zealand Synchrotron Group and the Australian Synchrotron. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.