2wks | pdb_00002wks

Structure of Helicobacter pylori Type II Dehydroquinase with a new carbasugar-thiophene inhibitor.

spinqualitylabelsall models 2wks, resolution 2.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wks is a 6 chain structure with sequence from Helicobacter pylori. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.95Å Ligands: CB6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AROQ_HELPY 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 shikimic acid pathway is essential to many pathogens but absent in mammals. Enzymes in its pathway are therefore appropriate targets for the development of novel antibiotics. Dehydroquinase is the third enzyme of the pathway, catalyzing the reversible dehydratation of 3-dehydroquinic acid to form 3-dehydroshikimic acid. Here we present the synthesis of novel inhibitors with high affinity for Helicobacter pylori type II dehydroquinase and efficient inhibition characteristics. The structure of Helicobacter pylori type II dehydroquinase in complex with the most potent inhibitor shows that the aromatic functional group interacts with the catalytic Tyr22 by pi-stacking, expelling the Arg17 side chain, which is essential for catalysis, from the active site. The structure therefore explains the favorable properties of the inhibitor and will aid in design of improved antibiotics. Synthesis and Biological Evaluation of New Nanomolar Competitive Inhibitors of Helicobacter pylori Type II Dehydroquinase. Structural Details of the Role of the Aromatic Moieties with Essential Residues (double dagger).,Prazeres VF, Tizon L, Otero JM, Guardado-Calvo P, Llamas-Saiz AL, van Raaij MJ, Castedo L, Lamb H, Hawkins AR, Gonzalez-Bello C J Med Chem. 2009 Nov 13. PMID:19911771 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dehydroquinase 3D structures

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