View source for 13ea


==X-ray crystal structure of human biliverdin beta IX reductase in complex with NADP and BCT002066==
<StructureSection load='13ea' size='340' side='right'caption='[[13ea]], [[Resolution|resolution]] 1.74&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[13ea]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=13EA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=13EA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.74&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1DFJ:(3M)-3-[(8R)-3-cyclopropyl-2-(furan-2-yl)-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-5-yl]benzoic+acid'>A1DFJ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=13ea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=13ea OCA], [https://pdbe.org/13ea PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=13ea RCSB], [https://www.ebi.ac.uk/pdbsum/13ea PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=13ea ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BLVRB_HUMAN 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.<ref>PMID:10620517</ref> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:42505148</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 13ea" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kreitler DF]]