7er6: Difference between revisions
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==Crystal structure of human Biliverdin IX-beta reductase B== | |||
<StructureSection load='7er6' size='340' side='right'caption='[[7er6]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7er6]] 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=7ER6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ER6 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]] 1.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7er6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7er6 OCA], [https://pdbe.org/7er6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7er6 RCSB], [https://www.ebi.ac.uk/pdbsum/7er6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7er6 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 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 (<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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7er6" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Flavin reductase|Flavin reductase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Griesinger C]] | |||
[[Category: Ha JH]] | |||
[[Category: Kim M]] | |||
[[Category: Lee D]] | |||
[[Category: Ryu KS]] | |||
Latest revision as of 20:00, 29 November 2023
Crystal structure of human Biliverdin IX-beta reductase BCrystal structure of human Biliverdin IX-beta reductase B
Structural highlights
FunctionBLVRB_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.[1] Publication Abstract from PubMedBiliverdin 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 (<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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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