13eb | pdb_000013eb

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

spinqualitylabelsall models 13eb, resolution 1.82Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 13eb is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.82Å Ligands: A1DFK, GOL, NAP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BLVRB_HUMAN Broad specificity oxidoreductase that catalyzes the NADPH-dependent reduction of a variety of flavins, such as riboflavin, FAD or FMN, biliverdins, methemoglobin and PQQ (pyrroloquinoline quinone). Contributes to heme catabolism and metabolizes linear tetrapyrroles. Can also reduce the complexed Fe(3+) iron to Fe(2+) in the presence of FMN and NADPH. In the liver, converts biliverdin to bilirubin. Publication Abstract from PubMed 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. In vitro 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. A Structure-guided Active Site Affinity Ligand Unmasks a Stress-Sensitizing Role for BLVRB in the Endoplasmic Reticulum.,Thekke Veedu RR, Sheriff J, Nesbitt NM, Marchenko N, Pennacchia L, Ginex T, Hearing P, Kreitler DF, Bahou WF J Med Chem. 2026 Jul 27. doi: 10.1021/acs.jmedchem.6c01466. PMID:42505148 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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