Crystal structure of chorismate synthase: a novel FMN-binding protein fold and functional insights

J Mol Biol. 2004 Feb 27;336(4):903-15. doi: 10.1016/j.jmb.2003.12.072.

Abstract

Chorismate synthase catalyzes the conversion of 5-enolpyruvylshikimate 3-phosphate to chorismate in the shikimate pathway, which represents an attractive target for discovering antimicrobial agents and herbicides. Chorismate serves as a common precursor for the synthesis of aromatic amino acids and many aromatic compounds in microorganisms and plants. Chorismate synthase requires reduced FMN as a cofactor but the catalyzed reaction involves no net redox change. Here, we have determined the crystal structure of chorismate synthase from Helicobacter pylori in both FMN-bound and FMN-free forms. It is a tetrameric enzyme, with each monomer possessing a novel "beta-alpha-beta sandwich fold". Highly conserved regions, including several flexible loops, cluster together around the bound FMN to form the active site. The unique FMN-binding site is formed largely by a single subunit, with a small contribution from a neighboring subunit. The isoalloxazine ring of the bound FMN is significantly non-planar. Our structure illuminates the essential functional roles played by the cofactor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Crystallography, X-Ray
  • Flavin Mononucleotide / metabolism
  • Flavoproteins / chemistry*
  • Flavoproteins / metabolism
  • Helicobacter pylori / enzymology
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphorus-Oxygen Lyases / chemistry*
  • Phosphorus-Oxygen Lyases / metabolism
  • Protein Binding
  • Protein Conformation*
  • Protein Folding
  • Protein Structure, Quaternary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Sequence Alignment
  • Shikimic Acid / metabolism

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • FMN-binding protein, Desulfovibrio vulgaris
  • Flavoproteins
  • Protein Subunits
  • Shikimic Acid
  • Flavin Mononucleotide
  • chorismate synthase
  • Phosphorus-Oxygen Lyases

Associated data

  • PDB/1UM0
  • PDB/1UMF