8K4K
Crystal structure of human Biliverdin IX-beta reductase B with Olsalazine carbon derivative
Summary for 8K4K
| Entry DOI | 10.2210/pdb8k4k/pdb |
| Descriptor | Flavin reductase (NADPH), GLYCEROL, SULFATE ION, ... (6 entities in total) |
| Functional Keywords | platelets, nadp, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 46848.47 |
| Authors | Ha, J.H.,Jung, H.M.,dela Cerna, M.V.C.,Burlison, J.A.,Lee, D.,Ryu, K.S. (deposition date: 2023-07-19, release date: 2025-01-22, Last modification date: 2025-01-29) |
| Primary citation | Jung, H.M.,Ha, J.H.,Dela Cerna, M.V.C.,Burlison, J.A.,Choi, J.,Kim, B.R.,Bang, J.K.,Ryu, K.S.,Lee, D. An Innovative Inhibitor with a New Chemical Moiety Aimed at Biliverdin IX beta Reductase for Thrombocytopenia and Resilient against Cellular Degradation. Pharmaceutics, 16:-, 2024 Cited by PubMed Abstract: Biliverdin IXβ reductase (BLVRB) has emerged as a promising therapeutic target for thrombocytopenia due to its involvement in reactive oxygen species (ROS) mechanisms. During the pursuit of inhibitors targeting BLVRB, olsalazine (OSA) became apparent as one of the most potent candidates. However, the direct application of OSA as a BLVRB inhibitor faces challenges, as it is prone to degradation into 5-aminosalicylic acid through cleavage of the diazenyl bond by abundant azoreductase (AzoR) enzymes in gut microbiota and eukaryotic cells. To overcome this obstacle, we devised olsalkene (OSK), an inhibitor where the diazenyl bond in OSA has been substituted with an alkene bond. OSK not only matches the efficacy of OSA but also demonstrates improved stability against degradation by AzoR, presenting a promising solution to this limitation. Furthermore, we have found that both OSK and OSA inhibit BLVRB, regardless of the presence of nicotinamide adenine dinucleotide phosphate, unlike other known inhibitors. This discovery opens new avenues for investigating the roles of BLVRB in blood disorders, including thrombocytopenia. PubMed: 39339186DOI: 10.3390/pharmaceutics16091148 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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