The atomic resolution structure of human aldose reductase reveals that rearrangement of a bound ligand allows the opening of the safety-belt loop.

Article Details

Citation

Copy to clipboard

Biadene M, Hazemann I, Cousido A, Ginell S, Joachimiak A, Sheldrick GM, Podjarny A, Schneider TR

The atomic resolution structure of human aldose reductase reveals that rearrangement of a bound ligand allows the opening of the safety-belt loop.

Acta Crystallogr D Biol Crystallogr. 2007 Jun;63(Pt 6):665-72. Epub 2007 May 15.

PubMed ID

17505104 [ View in PubMed

]

Abstract

The crystal structure of human aldose reductase in complex with citrate has been determined to a resolution of 0.82 A. The difference electron density for H atoms unequivocally shows that the cofactor is in the oxidized state corresponding to the situation after the catalytic event has occurred. A citrate molecule bound to the active site has been modelled in two different conformations. These two conformations correlate with a fully closed and a partially open conformation of the so-called safety-belt loop (Gly213-Ser226). The open conformation is observed for the first time with the cofactor bound to the protein and may be related to the initial phase of the opening of the safety belt. The structure suggests that after the catalytic event, a rearrangement of a bound ligand can trigger the opening of the safety-belt loop, thus initiating the release of the oxidized cofactor.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Citric acid	Aldose reductase	Protein	Humans	Yes	Inhibitor	Details

Polypeptides

Name	UniProt ID
Aldose reductase	P15121	Details