InterPro domain: IPR035904

Chorismate synthase (CS; 5-enolpyruvylshikimate-3-phosphate phospholyase; 1-carboxyvinyl-3-phosphoshikimate phosphate-lyase; E.C. 4.2.3.5) catalyzes the seventh and final step in the shikimate pathway which is used in prokaryotes, fungi and plants for the biosynthesis of aromatic amino acids. It catalyzes the 1,4-trans elimination of the phosphate group from 5-enolpyruvylshikimate-3-phosphate (EPSP) to form chorismate which can then be used in phenylalanine, tyrosine or tryptophan biosynthesis. Chorismate synthase requires the presence of a reduced flavin mononucleotide (FMNH2 or FADH2) for its activity. Chorismate synthase from various sources shows a high degree of sequence conservation [ 1 , 2 ]. It is a protein of about 360 to 400 amino-acid residues.

Depending on the capacity of these enzymes to regenerate the reduced form of FMN, chorismate synthases are divided into two groups: enzymes, mostly from plants and eubacteria, that sequester CS from the cellular environment, are monofunctional, while those that can generate reduced FMN at the expense of NADPH, such as found in fungi and the ciliated protozoan Euglena gracilis, are bifunctional, having an additional NADPH:FMN oxidoreductase activity. Recently, bifunctionality of the Mycobacterium tuberculosis enzyme (MtCS) was determined by measurements of both chorismate synthase and NADH:FMN oxidoreductase activities. Since shikimate pathway enzymes are present in bacteria, fungi and apicomplexan parasites (such as Toxoplasma gondii, Plasmodium falciparum, and Cryptosporidium parvum) but absent in mammals, they are potentially attractive targets for the development of new therapy against infectious diseases such as tuberculosis (TB) [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ].

The chorismate synthase AroC consists of two DCoH-like beta(2)-alpha-beta(2)-alpha structural repeats.

1. Molecular cloning and analysis of a cDNA coding for chorismate synthase from the higher plant Corydalis sempervirens Pers. J. Biol. Chem. 266, 21434-8
2. Molecular cloning, characterization and analysis of the regulation of the ARO2 gene, encoding chorismate synthase, of Saccharomyces cerevisiae. Mol. Microbiol. 5, 2143-52
3. Chorismate synthase: an attractive target for drug development against orphan diseases. Curr Drug Targets 8, 437-44
4. Conservation of NADPH utilization by chorismate synthase and its implications for the evolution of the shikimate pathway. Mol. Microbiol. 65, 1249-57
5. Escherichia coli chorismate synthase. Biochem. Soc. Trans. 24, 84-8
6. Replacement of two invariant serine residues in chorismate synthase provides evidence that a proton relay system is essential for intermediate formation and catalytic activity. FEBS J. 275, 1464-73
7. Crystal structure of the bifunctional chorismate synthase from Saccharomyces cerevisiae. J. Biol. Chem. 279, 619-25
8. Structure of chorismate synthase from Mycobacterium tuberculosis. J. Struct. Biol. 154, 130-43
9. Crystal structure of chorismate synthase from Aquifex aeolicus reveals a novel beta alpha beta sandwich topology. Proteins 54, 166-9
10. Crystal structure of chorismate synthase: a novel FMN-binding protein fold and functional insights. J. Mol. Biol. 336, 903-15
11. The structure of chorismate synthase reveals a novel flavin binding site fundamental to a unique chemical reaction. Structure 11, 1499-511
12. Mutagenic analysis of an invariant aspartate residue in chorismate synthase supports its role as an active site base. Biochemistry 46, 3768-74