3nnt

Crystal Structure of K170M Mutant of Type I 3-Dehydroquinate Dehydratase (aroD) from Salmonella typhimurium LT2 in Non-Covalent Complex with Dehydroquinate.

spinqualitylabelsall models 3nnt, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3nnt is a 2 chain structure with sequence from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.6Å Ligands: DQA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AROD_SALTY 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 biosynthetic shikimate pathway consists of seven enzymes that catalyze sequential reactions to generate chorismate, a critical branch point in the synthesis of the aromatic amino acids. The third enzyme in the pathway, dehydroquinate dehydratase (DHQD), catalyzes the dehydration of 3-dehydroquinate to 3-dehydroshikimate. We present three crystal structures of the type I DHQD from the intestinal pathogens Clostridium difficile and Salmonella enterica. Structures of the enzyme with substrate and covalent pre- and post-dehydration reaction intermediates provide snapshots of successive steps along the type I DHQD-catalyzed reaction coordinate. These structures reveal that the position of the substrate within the active site does not appreciably change upon Schiff base formation. The intermediate state structures reveal a reaction state-dependent behavior of His-143 in which the residue adopts a conformation proximal to the site of catalytic dehydration only when the leaving group is present. We speculate that His-143 is likely to assume differing catalytic roles in each of its observed conformations. One conformation of His-143 positions the residue for the formation/hydrolysis of the covalent Schiff base intermediates, whereas the other conformation positions the residue for a role in the catalytic dehydration event. The fact that the shikimate pathway is absent from humans makes the enzymes of the pathway potential targets for the development of non-toxic antimicrobials. The structures and mechanistic insight presented here may inform the design of type I DHQD enzyme inhibitors. Insights into the mechanism of type I dehydroquinate dehydratases from structures of reaction intermediates.,Light SH, Minasov G, Shuvalova L, Duban ME, Caffrey M, Anderson WF, Lavie A J Biol Chem. 2011 Feb 4;286(5):3531-9. Epub 2010 Nov 18. PMID:21087925 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dehydroquinase 3D structures

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