PDBsum entry 1deh

Oxidoreductase

PDB id: 1deh

Contents

Protein chain

374 a.a. *

Ligands

NAD-PYZ

NAD

PYZ

Metals

_ZN ×4

_CL

Waters ×314

* Residue conservation analysis

PDB id:

1deh

Name:

Oxidoreductase

Title:

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

Structure:

Human beta1 alcohol dehydrogenase. Chain: a, b. Synonym: beta1 adh. Engineered: yes. Other_details: the structure for homodimeric beta1 alcohol dehydrogenase was solved with one NAD+ and one 4-iodopyrazole per subunit

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: liver. Gene: human beta1 cdna. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: adh2 - standard convention is to denote the polymorphism with a 1 in superscript, i.E., Adh2==1==)

Biol. unit:

Dimer (from PQS)

Resolution:

2.20Å R-factor: 0.180 R-free: 0.261

Authors:

T.D.Hurley,G.J.Davis

Key ref:

G.J.Davis et al. (1996). X-ray structure of human beta3beta3 alcohol dehydrogenase. The contribution of ionic interactions to coenzyme binding. J Biol Chem, 271, 17057-17061. PubMed id: 8663387 DOI: 10.1074/jbc.271.29.17057

Date:

14-Oct-95 Release date: 08-Mar-96

Protein chains

P00325  (ADH1B_HUMAN) -  All-trans-retinol dehydrogenase [NAD(+)] ADH1B from Homo sapiens

Seq: 375 a.a.

Struc: 374 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.1.1.1.105 - all-trans-retinol dehydrogenase (NAD(+)).
• Reaction: all-trans-retinol--[retinol-binding protein] + NAD⁺ = all-trans- retinal--[retinol-binding protein] + NADH + H⁺

all-trans-retinol--[retinol-binding protein] + NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly) = all-trans- retinal--[retinol-binding protein] + NADH + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1074/jbc.271.29.17057

J Biol Chem 271:17057-17061 (1996)

PubMed id: 8663387

X-ray structure of human beta3beta3 alcohol dehydrogenase. The contribution of ionic interactions to coenzyme binding.

G.J.Davis, W.F.Bosron, C.L.Stone, K.Owusu-Dekyi, T.D.Hurley.

ABSTRACT

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.

Selected figure(s)

Figure 1.
Fig. 1. Electron density in the vicinity of residue 369. Omit 2F[o] F[c] electron density maps for (A) [3] ADH and (B) [1] ADH. Waters which occur between the amino acid at position 369 and coenzyme molecule are also displayed. The electron density maps were calculated after first removing those atoms displayed in the figure from the structure factor calculation. The maps are contoured at 1 S.D. of their respective electron density.

Figure 2.
Fig. 2. Aligned active sites of human [1] and [3] ADH. A stereo diagram of human [3] (thick lines) and [1] (thin lines) structures in the vicinity of amino acid 369. The structures were aligned by superposition of all their respective C atoms. R.m.s differences for alignment of [3] to [1] are 0.25 Å for all C atoms. Alignments of individual subunits or domains yielded r.m.s values of 0.19 Å for the C atoms within subunit A, 0.17 Å for the C atoms within the coenzyme domain, and 0.20 Å for the catalytic domain of the A subunits; the corresponding values for alignment of the B subunits are 0.25, 0.19, and 0.24 Å.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1996, 271, 17057-17061) copyright 1996.