9M3K
Crystal structure of GinKR1
Summary for 9M3K
| Entry DOI | 10.2210/pdb9m3k/pdb |
| Descriptor | ketoreductase (2 entities in total) |
| Functional Keywords | short-chain dehydrogenase/reductase, ketoreductase, biosynthetic protein |
| Biological source | Glycyrrhiza inflata |
| Total number of polymer chains | 4 |
| Total formula weight | 151852.12 |
| Authors | |
| Primary citation | Ye, L.,Wang, Z.L.,Xu, Z.Q.,Tian, Y.G.,Zhang, M.,Abe, I.,Ye, M. Elucidating the Biosynthetic Pathway and Mechanisms of Retrochalcones. J.Am.Chem.Soc., 147:29205-29214, 2025 Cited by PubMed Abstract: Chalcone is a privileged natural product skeleton for drug discovery, and retrochalcone represents a group of nonclassical chalcones with a distinctive oxygen substitution pattern. Echinatin, a hepatoprotective agent, is a retrochalcone derived from . Despite their initial discovery half a century ago, the biosynthetic mechanisms of retrochalcones have remained elusive. In this work, we identified a ketoreductase, GinKR1, which selectively catalyzes the reduction of the 1″-carbonyl group of the dibenzoylmethane precursor 2'--methyllicodione, followed by spontaneous dehydration to form the retrochalcone skeleton. Our findings reveal that the A and B rings of retrochalcones are derived from the shikimate and polyketide pathways, respectively, which are reversed to normal chalcones. In addition, O isotope labeling verifies that the carbonyl oxygen of retrochalcones is derived from the hydroxyl group introduced by a flavanone 2-hydroxylase. The complete biosynthetic pathway of echinatin was elucidated by identifying six enzymes from . Moreover, we determined the crystal structure of GinKR1 and identified a critical α10 helix responsible for its regioselectivity. With this α10 helix as a marker, we further discovered homologous genes of GinKR1 from 185 plant species. This study elucidates the biosynthetic pathway and underlying mechanisms of retrochalcones. PubMed: 40729162DOI: 10.1021/jacs.5c08070 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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