3bto | pdb_00003bto

HORSE LIVER ALCOHOL DEHYDROGENASE COMPLEXED TO NADH AND (1S,3S)3-BUTYLTHIOLANE 1-OXIDE

spinqualitylabelsall models 3bto, resolution 1.66Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3bto 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. Method: X-ray diffraction, Resolution 1.66Å Ligands: NAD, SSB, ZN 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 Thiolane 1-oxides are analogs of the carbonyl substrates that bind to the alcohol dehydrogenase-NADH complex and are potent uncompetitive inhibitors against alcohol [Chadha, V. K., et al. (1985) J. Med. Chem. 28, 36-40]. The four stereoisomers of 3-butylthiolane 1-oxide (BTO) were separated by chiral phase chromatography. CD and 1H-NMR spectra identified the enantiomeric pairs. 1H-NMR chemical shifts were assigned on the basis of COSY spectra of both diastereoisomers and confirmed by HMQC spectra. Coupling constants were determined through one-dimensional decoupling experiments. NMR with chiral shift reagents, Eu(hfc)3 [europium tris [3-[(heptafluoropropyl)hydroxymethylene]-(+)-camphorate]] or (R)-(-)-N-(3,5-dinitrobenzoyl)-alpha-methylbenzylamine, determined that the most inhibitory isomer is either 1S,3R or 1R,3S. The chemical shifts of protons in the thiolane 1-oxide ring were influenced by the whole structure and were not correlated with the computed Mulliken charges. X-ray crystallography at 2.1 and 1.66 A resolution of the ternary enzyme complexes with NADH demonstrated that the absolute configuration of the most inhibitory (Kii = 0.31 microM) stereoisomer is 1S,3R and the next best inhibitor (Kii = 0.73 microM) is 1S,3S. The thiolane 1-oxide rings bind in the same position, in the substrate binding site, but the geometry of the complexes suggests that the sulfoxides are not transition state analogs. Significantly, the butyl groups of the two isomers are accommodated differently by flexible amino acid side chains adopting alternative rotameric conformations. Flexibility of liver alcohol dehydrogenase in stereoselective binding of 3-butylthiolane 1-oxides.,Cho H, Ramaswamy S, Plapp BV Biochemistry. 1997 Jan 14;36(2):382-9. PMID:9003191 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Alcohol dehydrogenase 3D structures

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