Novel NADPH-binding domain revealed by the crystal structure of aldose reductase
| Autor: | J.-M. Rondeau, Alberto Podjarny, F. Tête-Favier, Dino Moras, Patrick Barth, J.-F. Biellmann, J.-M. Reymann |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
chemistry.chemical_classification
Models Molecular Aldose reductase Multidisciplinary Binding Sites biology Stereochemistry Macromolecular Substances Protein Conformation Nicotinamide adenine dinucleotide Cofactor chemistry.chemical_compound Enzyme Polyol pathway Biochemistry chemistry X-Ray Diffraction Aldehyde Reductase biology.protein NADPH binding Binding site Protein secondary structure Oxidation-Reduction NADP |
| Zdroj: | Nature. 355(6359) |
| ISSN: | 0028-0836 |
| Popis: | Aldose reductase is the first enzyme in the polyol pathway and catalyses the NADPH-dependent reduction of D-glucose to D-sorbitol. Under normal physiological conditions aldose reductase participates in osmoregulation, but under hyperglycaemic conditions it contributes to the onset and development of severe complications in diabetes. Here we present the crystal structure of pig lens aldose reductase refined to an R-factor of 0.232 at 2.5-A resolution. It exhibits a single domain folded in an eight-stranded parallel alpha/beta barrel, similar to that in triose phosphate isomerase and a score of other enzymes. Hence, aldose reductase does not possess the expected canonical dinucleotide-binding domain. Crystallographic analysis of the binding of 2'-monophospho-adenosine-5'-diphosphoribose, which competitively inhibits NADPH binding reveals that it binds into a cleft located at the C-terminal end of the strands of the alpha/beta barrel. This represents a new type of binding for nicotinamide adenine dinucleotide coenzymes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|