7ERC
Crystal structure of human Biliverdin IX-beta reductase B with Deferasirox (ICL)
Summary for 7ERC
| Entry DOI | 10.2210/pdb7erc/pdb |
| Descriptor | Flavin reductase (NADPH), NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]benzoic acid, ... (5 entities in total) |
| Functional Keywords | platelets, biliverdin reductase b, blvrb, inhibitors, nadp, deferasirox, oxidoreductase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 46252.93 |
| Authors | Griesinger, C.,Lee, D.,Ryu, K.S.,Kim, M.,Ha, J.H. (deposition date: 2021-05-06, release date: 2022-01-19, Last modification date: 2023-11-29) |
| Primary citation | Kim, M.,Ha, J.H.,Choi, J.,Kim, B.R.,Gapsys, V.,Lee, K.O.,Jee, J.G.,Chakrabarti, K.S.,de Groot, B.L.,Griesinger, C.,Ryu, K.S.,Lee, D. Repositioning Food and Drug Administration-Approved Drugs for Inhibiting Biliverdin IX beta Reductase B as a Novel Thrombocytopenia Therapeutic Target. J.Med.Chem., 65:2548-2557, 2022 Cited by PubMed Abstract: Biliverdin IXβ reductase B (BLVRB) has recently been proposed as a novel therapeutic target for thrombocytopenia through its reactive oxygen species (ROS)-associated mechanism. Thus, we aim at repurposing drugs as new inhibitors of BLVRB. Based on IC (<5 μM), we have identified 20 compounds out of 1496 compounds from the Food and Drug Administration (FDA)-approved library and have clearly mapped their binding sites to the active site. Furthermore, we show the detailed BLVRB-binding modes and thermodynamic properties (Δ, Δ, and ) with nuclear magnetic resonance (NMR) and isothermal titration calorimetry together with complex structures of eight water-soluble compounds. We anticipate that the results will serve as a novel platform for further in-depth studies on BLVRB effects for related functions such as ROS accumulation and megakaryocyte differentiation, and ultimately treatments of platelet disorders. PubMed: 34957824DOI: 10.1021/acs.jmedchem.1c01664 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
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