Crystal structure of the vertebrate NADP(H)-dependent alcohol dehydrogenase (ADH8)
| Autor: | Ignacio Fita, Wendy F. Ochoa, Jaume Farrés, Albert Rosell, Eva Valencia, Xavier Parés |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Models
Molecular Ranidae Stereochemistry Protein Conformation NADP(H) Crystallography X-Ray Aldehyde Cofactor chemistry.chemical_compound Structural Biology Oxidoreductase medicine Animals Molecular Biology Alcohol dehydrogenase chemistry.chemical_classification Ethanol Binding Sites biology NAD(H) Lysine Alcohol Dehydrogenase Triad (anatomy) Alcohol Oxidoreductases Enzyme medicine.anatomical_structure chemistry Biochemistry Amphibian ADH Crystal structures biology.protein Alcohol dehydrogenases NAD+ kinase Protons NADP |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 0022-2836 |
| Popis: | The amphibian enzyme ADH8, previously named class IV-like, is the only known vertebrate alcohol dehydrogenase (ADH) with specificity towards NADP(H). The three-dimensional structures of ADH8 and of the binary complex ADH8-NADP+ have been now determined and refined to resolutions of 2.2Å and 1.8Å, respectively. The coenzyme and substrate specificity of ADH8, that has 50-65% sequence identity with vertebrate NAD(H)-dependent ADHs, suggest a role in aldehyde reduction probably as a retinal reductase. The large volume of the substrate-binding pocket can explain both the high catalytic efficiency of ADH8 with retinoids and the high Km value for ethanol. Preference of NADP(H) appears to be achieved by the presence in ADH8 of the triad Gly223-Thr224-His225 and the recruitment of conserved Lys228, which define a binding pocket for the terminal phosphate group of the cofactor. NADP(H) binds to ADH8 in an extended conformation that superimposes well with the NAD(H) molecules found in NAD(H)-dependent ADH complexes. No additional reshaping of the dinucleotide-binding site is observed which explains why NAD(H) can also be used as a cofactor by ADH8. The structural features support the classification of ADH8 as an independent ADH class. © 2003 Published by Elsevier Science Ltd. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect