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.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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