8FEV

Flavanone 4-Reductase from Sorghum bicolor-NADP(H) and dihydroquercetin complex

Summary for 8FEV

• Entry DOI: 10.2210/pdb8fev/pdb
• Descriptor: 3-deoxyanthocyanidin synthase, (2R,3R)-2-(3,4-DIHYDROXYPHENYL)-3,5,7-TRIHYDROXY-2,3-DIHYDRO-4H-CHROMEN-4-ONE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total)
• Functional Keywords: sdr type protein, flavanone, sorghum, oxidoreductase
• Biological source: Sorghum bicolor (sorghum)
• Total number of polymer chains: 2
• Total formula weight: 78261.79

Authors

Zhang, B.,Kang, C. (deposition date: 2022-12-06, release date: 2023-09-20, Last modification date: 2023-10-11)

Primary citation

Lewis, J.A.,Zhang, B.,Harza, R.,Palmer, N.,Sarath, G.,Sattler, S.E.,Twigg, P.,Vermerris, W.,Kang, C.
Structural Similarities and Overlapping Activities among Dihydroflavonol 4-Reductase, Flavanone 4-Reductase, and Anthocyanidin Reductase Offer Metabolic Flexibility in the Flavonoid Pathway.
Int J Mol Sci, 24:-, 2023

PubMed Abstract: Flavonoids are potent antioxidants that play a role in defense against pathogens, UV-radiation, and the detoxification of reactive oxygen species. Dihydroflavonol 4-reductase (DFR) and flavanone 4-reductase (FNR) reduce dihydroflavonols and flavanones, respectively, using NAD(P)H to produce flavan-(3)-4-(di)ols in flavonoid biosynthesis. Anthocyanidin reductase (ANR) reduces anthocyanidins to flavan-3-ols. In addition to their sequences, the 3D structures of recombinant DFR, FNR and ANR from sorghum and switchgrass showed a high level of similarity. The catalytic mechanism, substrate-specificity and key residues of three reductases were deduced from crystal structures, site-directed mutagenesis, molecular docking, kinetics, and thermodynamic ana-lyses. Although DFR displayed its highest activity against dihydroflavonols, it also showed activity against flavanones and anthocyanidins. It was inhibited by the flavonol quercetin and high concentrations of dihydroflavonols/flavonones. SbFNR1 and SbFNR2 did not show any activity against dihydroflavonols. However, SbFNR1 displayed activity against flavanones and ANR activity against two anthocyanidins, cyanidin and pelargonidin. Therefore, SbFNR1 and SbFNR2 could be specific ANR isozymes without delphinidin activity. Sorghum has high concentrations of 3-deoxyanthocyanidins in vivo, supporting the observed high activity of SbDFR against flavonols. Mining of expression data indicated substantial induction of these three reductase genes in both switchgrass and sorghum in response to biotic stress. Key signature sequences for proper DFR/ANR classification are proposed and could form the basis for future metabolic engineering of flavonoid metabolism.

PubMed: 37762209
DOI: 10.3390/ijms241813901

Experimental method

X-RAY DIFFRACTION (2.21 Å)