View source for 7erc


==Crystal structure of human Biliverdin IX-beta reductase B with Deferasirox (ICL)==
<StructureSection load='7erc' size='340' side='right'caption='[[7erc]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7erc]] is a 2 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=7ERC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ERC 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]] 1.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JBL:4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]benzoic+acid'>JBL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7erc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7erc OCA], [https://pdbe.org/7erc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7erc RCSB], [https://www.ebi.ac.uk/pdbsum/7erc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7erc 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> 
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== Publication Abstract from PubMed ==
Biliverdin IXbeta 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 IC50 (&lt;5 muM), 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 (DeltaH, DeltaS, and KD) 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.

Repositioning Food and Drug Administration-Approved Drugs for Inhibiting Biliverdin IXbeta Reductase B as a Novel Thrombocytopenia Therapeutic Target.,Kim M, Ha JH, Choi J, Kim BR, Gapsys V, Lee KO, Jee JG, Chakrabarti KS, de Groot BL, Griesinger C, Ryu KS, Lee D J Med Chem. 2021 Dec 27. doi: 10.1021/acs.jmedchem.1c01664. PMID:34957824<ref>PMID:34957824</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7erc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Flavin reductase|Flavin reductase]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Griesinger C]]
[[Category: Ha JH]]
[[Category: Kim M]]
[[Category: Lee D]]
[[Category: Ryu KS]]