1ZGD

Chalcone Reductase Complexed With NADP+ at 1.7 Angstrom Resolution

Summary for 1ZGD

• Entry DOI: 10.2210/pdb1zgd/pdb
• Descriptor: chalcone reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• Functional Keywords: polyketide, chalcone, deoxychalcone, isoflavonoid, biosynthesis, plant protein
• Biological source: Medicago sativa
• Total number of polymer chains: 2
• Total formula weight: 71359.04

Authors

Bomati, E.K.,Austin, M.B.,Bowman, M.E.,Dixon, R.A.,Noel, J.P. (deposition date: 2005-04-21, release date: 2005-06-28, Last modification date: 2023-08-23)

Primary citation

Bomati, E.K.,Austin, M.B.,Bowman, M.E.,Dixon, R.A.,Noel, J.P.
Structural elucidation of chalcone reductase and implications for deoxychalcone biosynthesis
J.Biol.Chem., 280:30496-30503, 2005

PubMed 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.

PubMed: 15970585
DOI: 10.1074/jbc.M502239200

Experimental method

X-RAY DIFFRACTION (1.7 Å)