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4psq

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Revision as of 11:25, 11 August 2016

Crystal Structure of Retinol-Binding Protein 4 (RBP4) in complex with a non-retinoid ligand

Structural highlights

4psq is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	3fmz
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[RET4_HUMAN] Defects in RBP4 are a cause of retinol-binding protein deficiency (RBP deficiency) [MIM:180250]. This condition causes night vision problems. It produces a typical 'fundus xerophthalmicus', featuring a progressed atrophy of the retinal pigment epithelium.

Function

[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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. Structure-assisted discovery of the first non-retinoid ligands for Retinol-Binding Protein 4. 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 doi:http://dx.doi.org/10.1016/j.bmcl.2014.04.089

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4psq"

@@ Line 1: / Line 1: @@
 ==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=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fmz|3fmz]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4psq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4psq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4psq RCSB], [http://www.ebi.ac.uk/pdbsum/4psq PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4psq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4psq OCA], [http://pdbe.org/4psq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4psq RCSB], [http://www.ebi.ac.uk/pdbsum/4psq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4psq ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 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|Retinol-binding protein]]
 == References ==
 <references/>

4psq

From Proteopedia

Revision as of 11:25, 11 August 2016

Crystal Structure of Retinol-Binding Protein 4 (RBP4) in complex with a non-retinoid ligand

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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