4BPS
Crystal structure of Chorismatase at 1.08 Angstrom resolution.
Summary for 4BPS
| Entry DOI | 10.2210/pdb4bps/pdb |
| Descriptor | FKBO, 3-(2-CARBOXYETHYL)BENZOIC ACID (3 entities in total) |
| Functional Keywords | hydrolase, yjgf fold |
| Biological source | STREPTOMYCES HYGROSCOPICUS SUBSP. ASCOMYCETICUS |
| Total number of polymer chains | 1 |
| Total formula weight | 37421.11 |
| Authors | Juneja, P.,Hubrich, F.,Diederichs, K.,Welte, W.,Andexer, J.N. (deposition date: 2013-05-28, release date: 2013-09-18, Last modification date: 2024-11-06) |
| Primary citation | Juneja, P.,Hubrich, F.,Diederichs, K.,Welte, W.,Andexer, J.N. Mechanistic Implications for the Chorismatase Fkbo Based on the Crystal Structure. J.Mol.Biol., 426:105-, 2014 Cited by PubMed Abstract: Chorismate-converting enzymes are involved in many biosynthetic pathways leading to natural products and can often be used as tools for the synthesis of chemical building blocks. Chorismatases such as FkbO from Streptomyces species catalyse the hydrolysis of chorismate yielding (dihydro)benzoic acid derivatives. In contrast to many other chorismate-converting enzymes, the structure and catalytic mechanism of a chorismatase had not been previously elucidated. Here we present the crystal structure of the chorismatase FkbO in complex with a competitive inhibitor at 1.08Å resolution. FkbO is a monomer in solution and exhibits pseudo-3-fold symmetry; the structure of the individual domains indicates a possible connection to the trimeric RidA/YjgF family and related enzymes. The co-crystallised inhibitor led to the identification of FkbO's active site in the cleft between the central and the C-terminal domains. A mechanism for FkbO is proposed based on both interactions between the inhibitor and the surrounding amino acids and an FkbO structure with chorismate modelled in the active site. We suggest that the methylene group of the chorismate enol ether takes up a proton from an active-site glutamic acid residue, thereby initiating chorismate hydrolysis. A similar chemistry has been described for isochorismatases, albeit implemented in an entirely different protein scaffold. This reaction model is supported by kinetic data from active-site variants of FkbO derived by site-directed mutagenesis. PubMed: 24036425DOI: 10.1016/J.JMB.2013.09.006 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.081 Å) |
Structure validation
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