7ERA

Crystal structure of human Biliverdin IX-beta reductase B with Olsalazine Sodium (OSS)

7ERA の概要

• エントリーDOI: 10.2210/pdb7era/pdb
• 分子名称: Flavin reductase (NADPH), NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 5-[(E)-(3-carboxy-4-oxidanyl-phenyl)diazenyl]-2-oxidanyl-benzoic acid, ... (5 entities in total)
• 機能のキーワード: platelets, biliverdin reductase b, blvrb, inhibitors, nadp, olsalazine sodium, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47240.65

構造登録者

Griesinger, C.,Lee, D.,Ryu, K.S.,Kim, M.,Ha, J.H. (登録日: 2021-05-06, 公開日: 2022-01-19, 最終更新日: 2023-11-29)

主引用文献

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

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: 34957824
DOI: 10.1021/acs.jmedchem.1c01664

実験手法

X-RAY DIFFRACTION (1.35 Å)