4myd

1.37 Angstrom Crystal Structure of E. Coli 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (MenH) in complex with SHCHC

spinqualitylabelsall models 4myd, resolution 1.37Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4myd is a 3 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.374Å Ligands: 164 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MENH_ECOLI Catalyzes a proton abstraction reaction that results in 2,5-elimination of pyruvate from 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC) and the formation of 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC). Is also able to catalyze the hydrolysis of the thioester bond in palmitoyl-CoA in vitro. Publication Abstract from PubMed The serine-histidine-aspartate triad is well known for its covalent, nucleophilic catalysis in a diverse array of enzymatic transformations. Here we show that its nucleophilicity is shielded and its catalytic role is limited to be a specific general base by an open-closed conformational change in the catalysis of 2-succinyl-6-hydroxy-2, 4-cyclohexadiene-1-carboxylate synthase (or MenH), a typical alpha/beta-hydrolase fold enzyme in the vitamin K biosynthetic pathway. This enzyme is found to adopt an open conformation without a functional triad in its ligand-free form and a closed conformation with a fully functional catalytic triad in the presence of its reaction product. The open-to-closed conformational transition involves movement of a half of the alpha-helical cap domain, which causes extensive structural changes in the alpha/beta-domain and forces the side chain of the triad histidine to adopt an energetically disfavored gauche-conformation to form the functional triad. NMR analysis shows that the inactive, open conformation without a triad prevails in ligand-free solution and is converted to the closed conformation with a properly formed triad by the reaction product. Mutation of the residues crucial to this open-closed transition either greatly decreases or completely eliminates the enzyme activity, supporting an important catalytic role for the structural change. These findings suggest that the open-closed conformational change tightly couple formation of the catalytic triad to substrate binding to enhance the substrate specificities and simultaneously shield the triad off its nucelophilicity, thus allowing it to expand its catalytic power beyond the nucleophilic catalysis. Molecular Basis of the General Base Catalysis of an alpha/beta-Hydrolase Catalytic Triad.,Sun Y, Yin S, Feng Y, Li J, Zhou J, Liu C, Zhu G, Guo Z J Biol Chem. 2014 Apr 15. PMID:24737327 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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