8JP2
Crystal structure of AKR1C1 in complex with DFV
Summary for 8JP2
| Entry DOI | 10.2210/pdb8jp2/pdb |
| Descriptor | Aldo-keto reductase family 1 member C1, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 7-HYDROXY-2-(4-HYDROXY-PHENYL)-CHROMAN-4-ONE, ... (4 entities in total) |
| Functional Keywords | aldo-keto reductase 1c1;20alpha-hydroxysteroid dehydrogenase; complex;inhibitor;flavanone, oxidoreductase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 37838.99 |
| Authors | |
| Primary citation | Liu, H.,Yao, Z.,Sun, M.,Zhang, C.,Huang, Y.Y.,Luo, H.B.,Wu, D.,Zheng, X. Inhibition of AKR1Cs by liquiritigenin and the structural basis. Chem.Biol.Interact., 385:110654-110654, 2023 Cited by PubMed Abstract: In vivo and in vitro studies have confirmed that liquiritigenin (LQ), the primary active component of licorice, acts as an antitumor agent. However, how LQ diminishes or inhibits tumor growth is not fully understood. Here, we report the enzymatic inhibition of LQ and six other flavanone analogues towards AKR1Cs (AKR1C1, AKR1C2 and AKR1C3), which are involved in prostate cancer, breast cancer, and resistance of anticancer drugs. Crystallographic studies revealed AKR1C3 inhibition of LQ is related to its complementarity with the active site and the hydrogen bonds net in the catalytic site formed through C-OH, aided by its nonplanar and compact structure due to the saturation of the CC double bond. Comparison of the LQ conformations in the structures of AKR1C1 and AKR1C3 revealed the induced-fit conformation changes, which explains the lack of isoform selectivity of LQ. Our findings will be helpful for better understanding the antitumor effects of LQ on hormonally dependent cancers and the rational design of selective AKR1Cs inhibitors. PubMed: 37666442DOI: 10.1016/j.cbi.2023.110654 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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