Chorismate mutase catalyzes the first committed step toward the biosynthesis of the
aromatic amino acids,
phenylalanine and
tyrosine. While this biosynthetic pathway exists exclusively in the cell cytoplasm, the Mycobacterium tuberculosis
enzyme has been shown to be secreted into the extracellular medium. The secretory nature of the
enzyme and its existence in M.
tuberculosis as a duplicated gene are suggestive of its role in host-pathogen interactions. We report here the crystal structure of homodimeric
chorismate mutase (Rv1885c) from M.
tuberculosis determined at 2.15 A resolution. The structure suggests possible gene duplication within each subunit of the dimer (residues 35-119 and 130-199) and reveals an interesting
proline-rich region on the
protein surface (residues 119-130), which might act as a recognition site for
protein-
protein interactions. The structure also offers an explanation for its regulation by small
ligands, such as
tryptophan, a feature previously unknown in the prototypical Escherichia coli
chorismate mutase. The
tryptophan ligand is found to be sandwiched between the two monomers in a dimer contacting residues 66-68. The active site in the "gene-duplicated" monomer is occupied by a
sulfate ion and is located in the first half of the
polypeptide, unlike in the Saccharomyces cerevisiae (yeast)
enzyme, where it is located in the later half. We hypothesize that the M.
tuberculosis chorismate mutase might have a role to play in host-pathogen interactions, making it an important target for designing inhibitor molecules against the deadly pathogen.