4guh | pdb_00004guh

1.95 Angstrom Crystal Structure of the Salmonella enterica 3-Dehydroquinate Dehydratase (aroD) E86A Mutant in Complex with Dehydroshikimate (Crystal Form #2)

spinqualitylabelsall models 4guh, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4guh 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 1.95Å Ligands: 3DS, NI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AROD_SALTY Publication Abstract from PubMed Dehydroquinate dehydratase (DHQD) catalyzes the third reaction in the biosynthetic shikimate pathway. Type I DHQDs are members of the greater aldolase superfamily, a group of enzymes that contain an active site lysine that forms a Schiff base intermediate. Three residues (Glu86, His143, and Lys170 in the Salmonella enterica DHQD) have previously been proposed to form a triad vital for catalysis. While the roles of Lys170 and His143 are well defined - Lys170 forms the Schiff base with the substrate and His143 shuttles protons in multiple steps in the reaction - the role of Glu86 remains poorly characterized. To probe Glu86's role, Glu86 mutants were generated and subjected to biochemical and structural study. The studies presented here demonstrate that mutant enzymes retain catalytic proficiency, calling into question the previously attributed role of Glu86 in catalysis and suggesting that His143 and Lys170 function as a catalytic dyad. Structures of the Glu86Ala (E86A) mutant in complex with covalently bound reaction intermediate reveal a conformational change of the His143 side chain. This indicates a predominant steric role for Glu86, to maintain the His143 side chain in position consistent with catalysis. The structures also explain why the E86A mutant is optimally active at more acidic conditions than the wild-type enzyme. In addition, a complex with the reaction product reveals a novel, likely non-productive, binding mode that suggests a mechanism of competitive product inhibition and a potential strategy for the design of therapeutics. Reassessing the type I dehydroquinate dehydratase catalytic triad: Kinetic and structural studies of Glu86 mutants.,Light SH, Anderson WF, Lavie A Protein Sci. 2013 Jan 23. doi: 10.1002/pro.2218. PMID:23341204 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dehydroquinase 3D structures

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