2jhf

Structural evidence for a ligand coordination switch in liver alcohol dehydrogenase

spinqualitylabelsall models 2jhf, resolution 1.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2jhf is a 2 chain structure with sequence from Equus caballus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1Å Ligands: CD, DMS, NAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ADH1E_HORSE 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 use of substrate analogues as inhibitors provides a way to understand and manipulate enzyme function. Here we report two 1 A resolution crystal structures of liver alcohol dehydrogenase in complex with NADH and two inhibitors: dimethyl sulfoxide and isobutyramide. Both structures present a dynamic state of inhibition. In the dimethyl sulfoxide complex structure, the inhibitor is caught in transition on its way to the active site using a flash-freezing protocol and a cadmium-substituted enzyme. One inhibitor molecule is partly located in the first and partly in the second coordination sphere of the active site metal. A hydroxide ion bound to the active site metal lies close to the pyridine ring of NADH, which is puckered in a twisted boat conformation. The cadmium ion is coordinated by both the hydroxide ion and the inhibitor molecule, providing structural evidence of a coordination switch at the active site metal ion. The structure of the isobutyramide complex reveals the partial formation of an adduct between the isobutyramide inhibitor and NADH. It provides evidence of the contribution of a shift from the keto to the enol tautomer during aldehyde reduction. The different positions of the inhibitors further refine the knowledge of the dynamics of the enzyme mechanism and explain how the crowded active site can facilitate the presence of a substrate and a metal-bound hydroxide ion. Structural evidence for a ligand coordination switch in liver alcohol dehydrogenase.,Meijers R, Adolph HW, Dauter Z, Wilson KS, Lamzin VS, Cedergren-Zeppezauer ES Biochemistry. 2007 May 8;46(18):5446-54. Epub 2007 Apr 13. PMID:17429946 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Alcohol dehydrogenase 3D structures

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