4gdm

Crystal Structure of E.coli MenH

spinqualitylabelsall models 4gdm, resolution 2.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4gdm 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. Ligands: CL, GOL, SO4 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 Recent revision of the biosynthetic pathway for menaquinone has led to the discovery of a previously unrecognized enzyme 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase, also known as MenH. This enzyme has an alpha/beta hydrolase fold with a catalytic triad comprising Ser86, His232, and Asp210. Mutational studies identified a number of conserved residues of importance to activity, and modeling further implicated the side chains of Tyr85 and Trp147 in formation of a non-standard oxyanion hole. We have solved the structure of E. coli MenH (EcMenH) at 2.75 A resolution, together with the structures of the active site mutant proteins Tyr85Phe and Arg124Ala, both at 2.5 A resolution. EcMenH has the predicted alpha/beta hydrolase fold with its core alpha/beta domain capped by a helical lid. The active site, a long groove beneath the cap, contains a number of conserved basic residues and is found to bind exogeneous anions, modeled as sulfate and chloride, in all three crystal structures. Docking studies with the MenH substrate and a transition state model indicate that the bound anions mark the binding sites for anionic groups on the substrate. The docking studies, and careful consideration of the active site geometry, further suggest that the oxyanion hole is of a conventional nature, involving peptide NH groups, rather than the proposed site involving Tyr85 and Trp147. This is in accord with conclusions from the structure of S. aureus MenH. Comparisons with the latter do, however, indicate differences in the periphery of the active site that could be of relevance to selective inhibition of MenH enzymes. Crystal Structures of E. coli Native MenH and Two Active Site Mutants.,Johnston JM, Jiang M, Guo Z, Baker EN PLoS One. 2013 Apr 18;8(4):e61325. doi: 10.1371/journal.pone.0061325. Print 2013. PMID:23637813 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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