Crystal structure of chorismate synthase: a novel FMN-binding protein fold and functional insights.
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.
Ahn
Hyung Jun
HJ
Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-0742, South Korea.
Yoon
Hye-Jin
HJ
Lee
Byung
B
Suh
Se Won
SW
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D005486:Flavin Mononucleotide / Q000378:metabolism; D005420:Flavoproteins / Q000737:chemistry* / Q000378:metabolism; D016480:Helicobacter pylori / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019761:Phosphorus-Oxygen Lyases / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D012765:Shikimic Acid / Q000378:metabolism
D001426:Bacterial Proteins; D002352:Carrier Proteins; C086046:FMN-binding protein, Desulfovibrio vulgaris; D005420:Flavoproteins; D021122:Protein Subunits; D012765:Shikimic Acid; D005486:Flavin Mononucleotide; C019895:chorismate synthase; D019761:Phosphorus-Oxygen Lyases