1deh

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spinqualitylabelsall models 1deh, resolution 2.2Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTALLIZATION OF HUMAN BETA1 ALCOHOL DEHYDROGENASE (15 MG/ML) IN 50 MM SODIUM PHOSPHATE (PH 7.5), 2.0 MM NAD+ AND 1 MM 4-IODOPYRAZOLE AT 25 OC, 13% (W/V) PEG 8000

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The three-dimensional structure of the human beta3beta3 dimeric alcohol, dehydrogenase (beta3) was determined to 2.4-A resolution. beta3 was, crystallized as a ternary complex with the coenzyme NAD+ and the, competitive inhibitor 4-iodopyrazole. beta3 is a polymorphic variant at, ADH2 that differs from beta1 by a single amino acid substitution of, Arg-369 --> Cys. The available x-ray structures of mammalian alcohol, dehydrogenases show that the side chain of Arg-369 forms an ion pair with, the NAD(H) pyrophosphate to stabilize the E.NAD(H) complex. The Cys-369, side chain of beta3 cannot form this interaction. The three-dimensional, structures of beta3 and beta1 are virtually identical, with the exception, that Cys-369 and two water molecules in beta3 occupy the position of, Arg-369 in beta1. The two waters occupy the same positions as two, guanidino nitrogens of Arg-369. Hence, the number of hydrogen bonding, interactions between the enzyme and NAD(H) are the same for both, isoenzymes. However, beta3 differs from beta1 by the loss of the, electrostatic interaction between the NAD(H) pyrophosphate and the Arg-369, side chain. The equilibrium dissociation constants of beta3 for NAD+ and, NADH are 350-fold and 4000-fold higher, respectively, than those for, beta1. These changes correspond to binding free energy differences of 3.5, kcal/mol for NAD+ and 4.9 kcal/mol for NADH. Thus, the Arg-369 --> Cys, substitution of beta3 isoenzyme destabilizes the interaction between, coenzyme and beta3 alcohol dehydrogenase.

Disease

Known diseases associated with this structure: Alcoholism, susceptibility to OMIM:[103720]

About this Structure

1DEH is a Single protein structure of sequence from Homo sapiens with ZN, CL, NAD and PYZ as ligands. Active as Alcohol dehydrogenase, with EC number 1.1.1.1 Full crystallographic information is available from OCA.

Reference

X-ray structure of human beta3beta3 alcohol dehydrogenase. The contribution of ionic interactions to coenzyme binding., Davis GJ, Bosron WF, Stone CL, Owusu-Dekyi K, Hurley TD, J Biol Chem. 1996 Jul 19;271(29):17057-61. PMID:8663387

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