title: Crystal structure of vestitone reductase from alfalfa (Medicago sativa L.).
abstract: Isoflavonoids are commonly found in leguminous plants, where they play important roles in plant defense and have significant health benefits for animals and humans. Vestitone reductase catalyzes a stereospecific NADPH-dependent reduction of (3R)-vestitone in the biosynthesis of the antimicrobial isoflavonoid phytoalexin medicarpin. The crystal structure of alfalfa (Medicago sativa L.) vestitone reductase has been determined at 1.4 A resolution. The structure contains a classic Rossmann fold domain in the N terminus and a small C-terminal domain. Sequence and structural analysis showed that vestitone reductase is a member of the short-chain dehydrogenase/reductase (SDR) superfamily despite the low levels of sequence identity, and the prominent structural differences from other SDR enzymes with known structures. The putative binding sites for the co-factor NADPH and the substrate (3R)-vestitone were defined and located in a large cleft formed between the N and C-terminal domains of enzyme. Potential key residues for enzyme activity were also identified, including the catalytic triad Ser129-Tyr164-Lys168. A molecular docking study showed that (3R)-vestitone, but not the (3S) isomer, forms favored interactions with the co-factor and catalytic triad, thus providing an explanation for the enzyme's strict substrate stereo-specificity.
authors: Plant Biology Division, Samuel Roberts Noble Foundation, 2510 Sam Noble Parkway, Ardmore, OK 73401, USA.
authors: Hui
authors: H
authors: Shao
authors: Richard A
authors: RA
authors: Dixon
authors: Xiaoqiang
authors: X
authors: Wang
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D003067:Coenzymes / Q000378:metabolism; D018360:Crystallography, X-Ray; D007529:Isoflavones / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D000455:Medicago sativa / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009249:NADP; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D003067:Coenzymes; D007529:Isoflavones; D008024:Ligands; C088468:sophorol; D009249:NADP; C071072:vestitone reductase; D044925:Oxidoreductases Acting on CH-CH Group Donors