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2JHG

Structural evidence for a ligand coordination switch in liver alcohol dehydrogenase

Summary for 2JHG
Entry DOI10.2210/pdb2jhg/pdb
Related1A71 1A72 1ADB 1ADC 1ADF 1ADG 1AXE 1AXG 1BTO 1HET 1HEU 1HF3 1HLD 1JU9 1LDE 1LDY 1MG0 1MGO 1N8K 1N92 1P1R 1QLH 1QLJ 1QV6 1QV7 1YE3 2JHF 2OHX 2OXI 3BTO 5ADH 6ADH 7ADH 8ADH
DescriptorALCOHOL DEHYDROGENASE E CHAIN, ZINC ION, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (5 entities in total)
Functional Keywordsoxidoreductase, metal coordination, nad, zinc, inhibition, acetylation, metal-binding, alcohol dehydrogenase
Biological sourceEQUUS CABALLUS (HORSE)
Total number of polymer chains2
Total formula weight81469.27
Authors
Meijers, R.,Adolph, H.W.,Dauter, Z.,Wilson, K.S.,Lamzin, V.S.,Cedergren-Zeppezauer, E.S. (deposition date: 2007-02-22, release date: 2007-04-24, Last modification date: 2023-12-13)
Primary citationMeijers, R.,Adolph, H.W.,Dauter, Z.,Wilson, K.S.,Lamzin, V.S.,Cedergren-Zeppezauer, E.S.
Structural Evidence for a Ligand Coordination Switch in Liver Alcohol Dehydrogenase
Biochemistry, 46:5446-, 2007
Cited by
PubMed Abstract: 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.
PubMed: 17429946
DOI: 10.1021/BI6023594
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.2 Å)
Structure validation

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