3C1T

Binding of two substrate analogue molecules to dihydroflavonol 4-reductase alters the functional geometry of the catalytic site

Summary for 3C1T

• Entry DOI: 10.2210/pdb3c1t/pdb
• Related: 2IOD 3BXX
• Descriptor: dihydroflavonol 4-reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 3,5,7-TRIHYDROXY-2-(3,4,5-TRIHYDROXYPHENYL)-4H-CHROMEN-4-ONE, ... (4 entities in total)
• Functional Keywords: short chain dehydrogenase reductase, rossmann fold, flavonoids, oxidoreductase
• Biological source: Vitis vinifera (wine grape)
• Total number of polymer chains: 4
• Total formula weight: 156296.88

Authors

Trabelsi, N.,Petit, P.,Granier, T.,Langlois d'Estaintot, B.,Delrot, S.,Gallois, B. (deposition date: 2008-01-24, release date: 2008-02-19, Last modification date: 2023-08-30)

Primary citation

Trabelsi, N.,Petit, P.,Manigand, C.,Langlois d'Estaintot, B.,Granier, T.,Chaudiere, J.,Gallois, B.
Structural evidence for the inhibition of grape dihydroflavonol 4-reductase by flavonols
Acta Crystallogr.,Sect.D, D64:883-891, 2008

PubMed Abstract: Dihydroflavonol 4-reductase (DFR) is a key enzyme of the flavonoid biosynthesis pathway which catalyses the NADPH-dependent reduction of 2R,3R-trans-dihydroflavonols to leucoanthocyanidins. The latter are the precursors of anthocyans and condensed tannins, two major classes of phenolic compounds that strongly influence the organoleptic properties of wine. DFR has been investigated in many plant species, but little was known about its structural properties until the three-dimensional structure of the Vitis vinifera enzyme complexed with NADP(+) and its natural substrate dihydroquercetin (DHQ) was described. In the course of the study of substrate specificity, crystals of DFR-NADP(+)-flavonol (myricetin and quercetin) complexes were obtained. Their structures exhibit major changes with respect to that of the abortive DFR-NADP(+)-DHQ complex. Two flavonol molecules bind to the catalytic site in a stacking arrangement and alter its geometry, which becomes incompatible with enzymatic activity. The X-ray structures of both DFR-NADP(+)-myricetin and DFR-NADP(+)-quercetin are reported together with preliminary spectroscopic data. The results suggest that flavonols could be inhibitors of the activity of DFR towards dihydroflavonols.

PubMed: 18645237
DOI: 10.1107/S0907444908017769

Experimental method

X-RAY DIFFRACTION (2.252 Å)