1HLD

STRUCTURES OF HORSE LIVER ALCOHOL DEHYDROGENASE COMPLEXED WITH NAD+ AND SUBSTITUTED BENZYL ALCOHOLS

Summary for 1HLD

• Entry DOI: 10.2210/pdb1hld/pdb
• Descriptor: ALCOHOL DEHYDROGENASE, ZINC ION, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (6 entities in total)
• Functional Keywords: oxidoreductase(ch-oh(d)-nad(a))
• Biological source: Equus caballus (horse)
• Cellular location: Cytoplasm: P00327
• Total number of polymer chains: 2
• Total formula weight: 82065.28

Authors

Ramaswamy, S.,Eklund, H.,Plapp, B.V. (deposition date: 1993-11-23, release date: 1994-10-15, Last modification date: 2024-02-07)

Primary citation

Ramaswamy, S.,Eklund, H.,Plapp, B.V.
Structures of horse liver alcohol dehydrogenase complexed with NAD+ and substituted benzyl alcohols.
Biochemistry, 33:5230-5237, 1994

PubMed Abstract: Structures of the enzyme complexed with NAD+ and 2,3,4,5,6-pentafluorobenzyl alcohol were determined by X-ray crystallography at a resolution of 2.1 A and to a refinement R value of 18.3% for a monoclinic (P2(1)) form and to 2.4 A and an R value of 18.9% for a triclinic crystal form. The pentafluorobenzyl alcohol does not react, due to electron withdrawal by the fluorine atoms. A structure with NAD+ and p-bromobenzyl alcohol in the monoclinic form was also determined at 2.5 A and an R value of 16.7%. The conformations of the subunits in the monoclinic and triclinic crystal forms are very similar. The dimer is the asymmetric unit, and a rigid body rotation closes the cleft between the coenzyme and catalytic domains upon complex formation. In the monoclinic form, this conformational change is described by a rotation of 9 degrees in one subunit and 10 degrees in the other. The pentafluoro- and p-bromobenzyl alcohols bind in overlapping positions. The hydroxyl group of each alcohol is ligated to the catalytic zinc and participates in an extensive hydrogen-bonded network that includes the imidazole group of His-51, which can act as a base and shuttle a proton to solvent. The hydroxymethyl carbon of the pentafluorobenzyl alcohol is 3.4 A from C4 of the nicotinamide ring, and the pro-R hydrogen is in a good position for direct transfer to C4. The p-bromobenzyl alcohol may react after small rotations around single bonds of the alcohol. These structures should approximate the active Michaelis-Menten complexes.

PubMed: 8172897
DOI: 10.1021/bi00183a028

Experimental method

X-RAY DIFFRACTION (2.1 Å)