PDBsum entry 1agn

Oxidoreductase

PDB id: 1agn

Contents

Protein chain

373 a.a. *

Ligands

ACT ×10

NAD ×4

Metals

_ZN ×16

Waters ×9

* Residue conservation analysis

PDB id:

1agn

Name:

Oxidoreductase

Title:

X-ray structure of human sigma alcohol dehydrogenase

Structure:

Human sigma alcohol dehydrogenase. Chain: a, b, c, d. Synonym: sigma adh. Engineered: yes. Other_details: the structure contains one NAD+ per subunit

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: stomach. Gene: human sigma cdna (adh7). Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: purchased from boeringer mannheim (indianapolis, in)

Biol. unit:

Dimer (from PQS)

Resolution:

3.00Å R-factor: 0.225 R-free: 0.305

Authors:

T.D.Hurley,P.Xie

Key ref:

P.Xie et al. (1997). X-ray structure of human class IV sigmasigma alcohol dehydrogenase. Structural basis for substrate specificity. J Biol Chem, 272, 18558-18563. PubMed id: 9228021 DOI: 10.1074/jbc.272.30.18558

Date:

04-Jun-96 Release date: 12-Mar-97

Protein chains

P40394  (ADH7_HUMAN) -  All-trans-retinol dehydrogenase [NAD(+)] ADH7 from Homo sapiens

Seq: 386 a.a.

Struc: 373 a.a.

Enzyme reactions

• Enzyme class 1: E.C.1.1.1.1 - alcohol dehydrogenase.
• Reaction:
  1. a primary alcohol + NAD⁺ = an aldehyde + NADH + H⁺
  2. a secondary alcohol + NAD⁺ = a ketone + NADH + H⁺

primary alcohol (Bound ligand (Het Group name = ACT) matches with 40.00% similarity) + NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly) = aldehyde + NADH + H(+)

secondary alcohol + NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly) = ketone + NADH + H(+)

• Cofactor: Zn(2+) or Fe cation
• Enzyme class 2: 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(+)

• Enzyme class 3: E.C.1.1.1.66 - omega-hydroxydecanoate dehydrogenase.
• Reaction: 10-hydroxydecanoate + NAD⁺ = 10-oxodecanoate + NADH + H⁺

10-hydroxydecanoate + NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly) = 10-oxodecanoate + NADH + H(+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1074/jbc.272.30.18558

J Biol Chem 272:18558-18563 (1997)

PubMed id: 9228021

X-ray structure of human class IV sigmasigma alcohol dehydrogenase. Structural basis for substrate specificity.

P.Xie, S.H.Parsons, D.C.Speckhard, W.F.Bosron, T.D.Hurley.

ABSTRACT

The structural determinants of substrate recognition in the human class IV, or sigmasigma, alcohol dehydrogenase (ADH) isoenzyme were examined through x-ray crystallography and site-directed mutagenesis. The crystal structure of sigmasigma ADH complexed with NAD+ and acetate was solved to 3-A resolution. The human beta1beta1 and sigmasigma ADH isoenzymes share 69% sequence identity and exhibit dramatically different kinetic properties. Differences in the amino acids at positions 57, 116, 141, 309, and 317 create a different topology within the sigmasigma substrate-binding pocket, relative to the beta1beta1 isoenzyme. The nicotinamide ring of the NAD(H) molecule, in the sigmasigma structure, appears to be twisted relative to its position in the beta1beta1 isoenzyme. In conjunction with movements of Thr-48 and Phe-93, this twist widens the substrate pocket in the vicinity of the catalytic zinc and may contribute to this isoenzyme's high Km for small substrates. The presence of Met-57, Met-141, and Phe-309 narrow the middle region of the sigmasigma substrate pocket and may explain the substantially decreased Km values with increased chain length of substrates in sigmasigma ADH. The kinetic properties of a mutant sigmasigma enzyme (sigma309L317A) suggest that widening the middle region of the substrate pocket increases Km by weakening the interactions between the enzyme and smaller substrates while not affecting the binding of longer alcohols, such as hexanol and retinol.

Selected figure(s)

Figure 1.
Fig. 1. Comparison of , , and [1] [1] dimers by alignment of their C atoms. All C atoms were used in the alignment. The^ result of the alignment using the CD dimer of ADH is shown. The other dimer of ADH in the asymmetric unit gives similar results.

Figure 2.
Fig. 2. The influence of the substitution of Ala-317 -Cys in on the conformation of the nicotinamide ring of NAD^+. The residues in ADH are shown using the thicker line. The electron density map is from the structure and contoured^ at 1.0 S.D. of the map.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1997, 272, 18558-18563) copyright 1997.

Figures were selected by an automated process.