1ldy

HORSE LIVER ALCOHOL DEHYDROGENASE COMPLEXED TO NADH AND CYCLOHEXYL FORMAMIDE (CXF)

spinqualitylabelsall models 1ldy, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1ldy is a 4 chain structure with sequence from Equus caballus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CXF, NAD, ZN Related: 3bto, 1lde Activity: Alcohol dehydrogenase, with EC number 1.1.1.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 Amides are analogs of aldehydes and potent inhibitors of liver alcohol dehydrogenases. They can be used for structural studies and for inhibiting the metabolism of alcohols that form toxic products. We studied N-alkyl amides that bind to the enzyme-NADH complex and act as uncompetitive inhibitors against varied concentrations of ethanol (millimolar Kii values, at pH 8 and 25 degrees C): N-propylacetamide (16), delta-valerolactam (1.6), N-formylpiperidine (0.14), N-isobutylformamide (0.028), N-(cyclohexylmethyl)-formamide (0.011), and N-cyclohexylformamide (0.0087). The lower affinity of delta-valerolactam and N-propylacetamide can be explained by steric hindrance with Phe93 of the enzyme. Replacing Phe93 with Ala in the S48T/F93A mutated enzyme, which resembles the natural alpha-isoenzyme of primates, improved binding of delta-valerolactam by 210-fold. The structures of horse liver enzyme complexed with NADH and N-cyclohexylformamide or N-formylpiperidine were determined by X-ray crystallography at 2.5 A resolution. In both complexes, the carbonyl oxygens of the inhibitors bind to the catalytic zinc and form a hydrogen bond to the hydroxyl group of Ser48 of the enzyme. The six-membered rings bind in overlapping, but rotated, positions that optimize hydrophobic interactions. The binding modes of the unreactive formamides appear to resemble the Michaelis complexes of the analogous substrates, with the re face of the carbonyl carbon suitably positioned to accept a hydrogen from NADH. Binding of formamides to liver alcohol dehydrogenase.,Ramaswamy S, Scholze M, Plapp BV Biochemistry. 1997 Mar 25;36(12):3522-7. PMID:9132002 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA