13EB

X-ray crystal structure of human biliverdin beta IX reductase in complex with NADP and BCT002109

これはPDB形式変換不可エントリーです。

13EB の概要

• エントリーDOI: 10.2210/pdb13eb/pdb
• 関連するPDBエントリー: 13DZ 13EA
• 分子名称: Flavin reductase (NADPH), NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, (3M)-3-{(2M,8S)-2-[3-(benzamidomethyl)phenyl]-3-ethyl-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-5-yl}benzoic acid, ... (5 entities in total)
• 機能のキーワード: nadp binding, heme degradation, thrombopoiesis, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23878.80

構造登録者

Kreitler, D.F. (登録日: 2026-05-01, 公開日: 2026-08-05)

主引用文献

Thekke Veedu, R.R.,Sheriff, J.,Nesbitt, N.M.,Marchenko, N.,Pennacchia, L.,Ginex, T.,Hearing, P.,Kreitler, D.F.,Bahou, W.F.
A Structure-guided Active Site Affinity Ligand Unmasks a Stress-Sensitizing Role for BLVRB in the Endoplasmic Reticulum.
J.Med.Chem., 2026

PubMed Abstract: Biliverdin IXb reductase (BLVRB) is an NAD(P)H-dependent oxidoreductase that regulates hematopoiesis and cellular stress, although measurement and sequelae of cellular active site engagement remain undefined. Here, we report the development of a nanoBRET platform enabling real-time BLVRB target engagement. Structure-guided design and chemical syntheses of BODIPY-labeled pyrazolopyrimidinone inhibitors generate cell-permeable acceptor ligands retaining high-affinity binding to the BLVRB active site. and cellular nanoBRET assays demonstrate specific energy transfer and inform equilibrium binding affinities, target engagement, and residence time analyses for diverse panels of BLVRB inhibitors. NanoBRET demonstrates strong concordance with enzymatic inhibition and is validated by crystallographic structures confirming active site binding. Live-cell imaging using affinity ligands reveals predominant endoplasmic reticulum localization and transient suppression of the ER stress chaperone GRP78/BiP without eliciting a canonical unfolded protein response. These studies inform a redox-regulated mechanism whereby spatiotemporal BLVRB active site engagement functions as a stress sensitizer modulating ER proteostasis.

PubMed: 42505148
DOI: 10.1021/acs.jmedchem.6c01466

実験手法

X-RAY DIFFRACTION (1.82 Å)