4bps | pdb_00004bps

Crystal structure of Chorismatase at 1.08 Angstrom resolution.

spinqualitylabelsall models 4bps, resolution 1.08Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bps is a 1 chain structure with sequence from Streptomyces hygroscopicus subsp. ascomyceticus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.081Å Ligands: 3EB, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FKBO_STRHY Involved in the biosynthesis of the macrocyclic amino acid-linked polyketides FK506 and FK520 which are potent immunosuppressants that prevent T-cell proliferation through initial binding to the immunophilin FKBP12. Catalyzes the hydrolysis of chorismate via a 1,4-conjugate elimination of water to yield (4R,5R)-4,5-dihydroxycyclohexa-1,5-dienecarboxylic acid (DCDC). Publication Abstract from PubMed 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 1.08A 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. Mechanistic Implications for the Chorismatase FkbO Based on the Crystal Structure.,Juneja P, Hubrich F, Diederichs K, Welte W, Andexer JN J Mol Biol. 2013 Sep 13. pii: S0022-2836(13)00575-5. doi:, 10.1016/j.jmb.2013.09.006. PMID:24036425 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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