13DZ
X-ray crystal structure of human biliverdin beta IX reductase in complex with NADP and BCT002104
This is a non-PDB format compatible entry.
Summary for 13DZ
| Entry DOI | 10.2210/pdb13dz/pdb |
| Descriptor | Flavin reductase (NADPH), NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, (3M)-3-[(2M,8S)-3-ethyl-2-(3-{[(3-methoxyphenyl)carbamamido]methyl}phenyl)-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-5-yl]benzoic acid, ... (5 entities in total) |
| Functional Keywords | nadp binding, heme degradation, thrombopoiesis, oxidoreductase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 23923.84 |
| Authors | |
| Primary citation | 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 Cited by 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: 42505148DOI: 10.1021/acs.jmedchem.6c01466 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.72 Å) |
Structure validation
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