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Structural elucidation of chalcone reductase and implications for deoxychalcone biosynthesis.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2005 Aug 26; Vol. 280 (34), pp. 30496-503. Date of Electronic Publication: 2005 Jun 21. - Publication Year :
- 2005
-
Abstract
- 4,2',4',6'-Tetrahydroxychalcone (chalcone) and 4,2',4'-trihydroxychalcone (deoxychalcone) serve as precursors of ecologically important flavonoids and isoflavonoids. Deoxychalcone formation depends on chalcone synthase and chalcone reductase; however, the identity of the chalcone reductase substrate out of the possible substrates formed during the multistep reaction catalyzed by chalcone synthase remains experimentally elusive. We report here the three-dimensional structure of alfalfa chalcone reductase bound to the NADP+ cofactor and propose the identity and binding mode of its substrate, namely the non-aromatized coumaryl-trione intermediate of the chalcone synthase-catalyzed cyclization of the fully extended coumaryl-tetraketide thioester intermediate. In the absence of a ternary complex, the quality of the refined NADP+-bound chalcone reductase structure serves as a template for computer-assisted docking to evaluate the likelihood of possible substrates. Interestingly, chalcone reductase adopts the three-dimensional structure of the aldo/keto reductase superfamily. The aldo/keto reductase fold is structurally distinct from all known ketoreductases of fatty acid biosynthesis, which instead belong to the short-chain dehydrogenase/reductase superfamily. The results presented here provide structural support for convergent functional evolution of these two ketoreductases that share similar roles in the biosynthesis of fatty acids/polyketides. In addition, the chalcone reductase structure represents the first protein structure of a member of the aldo/ketoreductase 4 family. Therefore, the chalcone reductase structure serves as a template for the homology modeling of other aldo/keto-reductase 4 family members, including the reductase involved in morphine biosynthesis, namely codeinone reductase.
- Subjects :
- Binding Sites
Chalcone chemistry
Chalcone metabolism
Chalcones
Chromatography, Gel
Crystallography, X-Ray
Esters metabolism
Evolution, Molecular
Fatty Acids chemistry
Fatty Acids metabolism
Medicago sativa enzymology
Models, Chemical
Models, Molecular
Mutagenesis, Site-Directed
NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases
NADP chemistry
Protein Binding
Protein Conformation
Protein Structure, Tertiary
Substrate Specificity
Alcohol Oxidoreductases chemistry
Chalcone analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 280
- Issue :
- 34
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15970585
- Full Text :
- https://doi.org/10.1074/jbc.M502239200