View source for 4psq


==Crystal Structure of Retinol-Binding Protein 4 (RBP4) in complex with a non-retinoid ligand==
<StructureSection load='4psq' size='340' side='right'caption='[[4psq]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4psq]] 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=4PSQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PSQ 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2WL:(1-BENZYL-1H-IMIDAZOL-4-YL)[4-(2-CHLOROPHENYL)PIPERAZIN-1-YL]METHANONE'>2WL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4psq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4psq OCA], [https://pdbe.org/4psq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4psq RCSB], [https://www.ebi.ac.uk/pdbsum/4psq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4psq ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/RET4_HUMAN RET4_HUMAN] Defects in RBP4 are a cause of retinol-binding protein deficiency (RBP deficiency) [MIM:[https://omim.org/entry/180250 180250]. This condition causes night vision problems. It produces a typical 'fundus xerophthalmicus', featuring a progressed atrophy of the retinal pigment epithelium.
== Function ==
[https://www.uniprot.org/uniprot/RET4_HUMAN RET4_HUMAN] Delivers retinol from the liver stores to the peripheral tissues. In plasma, the RBP-retinol complex interacts with transthyretin, this prevents its loss by filtration through the kidney glomeruli.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Retinol-Binding Protein 4 (RBP4) is a plasma protein that transports retinol (vitamin A) from the liver to peripheral tissues. This Letter highlights our efforts in discovering the first, to our knowledge, non-retinoid small molecules that bind to RBP4 at the retinol site and reduce serum RBP4 levels in mice, by disrupting the interaction between RBP4 and transthyretin (TTR), a plasma protein that binds RBP4 and protects it from renal excretion. Potent compounds were discovered and optimized quickly from high-throughput screen (HTS) hits utilizing a structure-based approach. Inhibitor co-crystal X-ray structures revealed unique disruptions of RBP4-TTR interactions by our compounds through induced loop conformational changes instead of steric hindrance exemplified by fenretinide. When administered to mice, A1120, a representative compound in the series, showed concentration-dependent retinol and RBP4 lowering.

Structure-assisted discovery of the first non-retinoid ligands for Retinol-Binding Protein 4.,Wang Y, Connors R, Fan P, Wang X, Wang Z, Liu J, Kayser F, Medina JC, Johnstone S, Xu H, Thibault S, Walker N, Conn M, Zhang Y, Liu Q, Grillo MP, Motani A, Coward P, Wang Z Bioorg Med Chem Lett. 2014 Jul 1;24(13):2885-91. doi: 10.1016/j.bmcl.2014.04.089., Epub 2014 May 2. PMID:24835984<ref>PMID:24835984</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4psq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Retinol-binding protein 3D structures|Retinol-binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Johnstone S]]
[[Category: Walker N]]
[[Category: Wang Z]]