Structural and functional characterization of Staphylococcus aureus dihydrodipicolinate synthase

FEBS Lett. 2008 Aug 20;582(19):2923-30. doi: 10.1016/j.febslet.2008.07.035. Epub 2008 Jul 29.

Abstract

Lysine biosynthesis is crucial for cell-wall formation in bacteria. Enzymes involved in lysine biosynthesis are thus potential targets for anti-microbial therapeutics. Dihydrodipicolinate synthase (DHDPS) catalyzes the first step of this pathway. Unlike its homologues, Staphylococcus aureus DHDPS is a dimer both in solution and in the crystal and is not feedback inhibited by lysine. The crystal structure of S. aureus DHDPS in the free and substrate bound forms provides a structural rationale for its catalytic mechanism. The structure also reveals unique conformational features of the S. aureus enzyme that could be crucial for the design of specific non-competitive inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Crystallography, X-Ray
  • Dimerization
  • Hydro-Lyases / antagonists & inhibitors
  • Hydro-Lyases / chemistry*
  • Hydro-Lyases / genetics
  • Lysine / biosynthesis
  • Molecular Sequence Data
  • Protein Conformation
  • Staphylococcus aureus / enzymology*
  • Staphylococcus aureus / genetics

Substances

  • Bacterial Proteins
  • Hydro-Lyases
  • 4-hydroxy-tetrahydrodipicolinate synthase
  • Lysine

Associated data

  • PDB/3DI0
  • PDB/3DI1