2xb8

Structure of Mycobacterium tuberculosis type II dehydroquinase in complex with inhibitor compound (2R)-2-(4-methoxybenzyl)-3- dehydroquinic acid

spinqualitylabelsall models 2xb8, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xb8 is a 1 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4, TRS, XNW Related: 1h0r, 1h05, 2dhq, 1h0s, 2xb9 Activity: 3-dehydroquinate dehydratase, with EC number 4.2.1.10 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [AROQ_MYCTU] Catalyzes a trans-dehydration via an enolate intermediate (By similarity).[HAMAP-Rule:MF_00169] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The binding mode of several substrate analogues, (2R)-2-benzyl-3-dehydroquinic acids 4, which are potent reversible competitive inhibitors of type II dehydroquinase (DHQ2), the third enzyme of the shikimic acid pathway, has been investigated by structural and computational studies. The crystal structures of Mycobacterium tuberculosis and Helicobacter pylori DHQ2 in complex with one of the most potent inhibitor, p-methoxybenzyl derivative 4 a, have been solved at 2.40 A and 2.75 A, respectively. This has allowed the resolution of the M. tuberculosis DHQ2 loop containing residues 20-25 for the first time. These structures show the key interactions of the aromatic ring in the active site of both enzymes and additionally reveal an important change in the conformation and flexibility of the loop that closes over substrate binding. The loop conformation and the binding mode of compounds 4 b-d has been also studied by molecular dynamics simulations, which suggest that the benzyl group of inhibitors 4 prevent appropriate orientation of the catalytic tyrosine of the loop for proton abstraction and disrupts its basicity. Understanding the Key Factors that Control the Inhibition of Type II Dehydroquinase by (2R)-2-Benzyl-3-dehydroquinic Acids.,Peon A, Otero JM, Tizon L, Prazeres VF, Llamas-Saiz AL, Fox GC, van Raaij MJ, Lamb H, Hawkins AR, Gago F, Castedo L, Gonzalez-Bello C ChemMedChem. 2010 Sep 2. PMID:20815012 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dehydroquinase 3D structures

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