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3fmz

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Revision as of 07:56, 5 December 2018

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

Structural highlights

3fmz is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	RBP4, PRO2222 (HUMAN)
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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Retinol-binding protein 4 (RBP4) transports retinol from the liver to extrahepatic tissues, and RBP4 lowering is reported to improve insulin sensitivity in mice. We have identified A1120, a high affinity (K(i) = 8.3 nm) non-retinoid ligand for RBP4, which disrupts the interaction between RBP4 and its binding partner transthyretin. Analysis of the RBP4-A1120 co-crystal structure reveals that A1120 induces critical conformational changes at the RBP4-transthyretin interface. Administration of A1120 to mice lowers serum RBP4 and retinol levels but, unexpectedly, does not improve insulin sensitivity. In addition, we show that Rpb4(-/-) mice display normal insulin sensitivity and are not protected from high fat diet-induced insulin resistance. We conclude that lowering RBP4 levels does not improve insulin sensitivity in mice. Therefore, RBP4 lowering may not be an effective strategy for treating diabetes.

Identification and characterization of a non-retinoid ligand for retinol-binding protein 4 which lowers serum retinol-binding protein 4 levels in vivo.,Motani A, Wang Z, Conn M, Siegler K, Zhang Y, Liu Q, Johnstone S, Xu H, Thibault S, Wang Y, Fan P, Connors R, Le H, Xu G, Walker N, Shan B, Coward P J Biol Chem. 2009 Mar 20;284(12):7673-80. Epub 2009 Jan 15. PMID:19147488^[1]

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

References

↑ Motani A, Wang Z, Conn M, Siegler K, Zhang Y, Liu Q, Johnstone S, Xu H, Thibault S, Wang Y, Fan P, Connors R, Le H, Xu G, Walker N, Shan B, Coward P. Identification and characterization of a non-retinoid ligand for retinol-binding protein 4 which lowers serum retinol-binding protein 4 levels in vivo. J Biol Chem. 2009 Mar 20;284(12):7673-80. Epub 2009 Jan 15. PMID:19147488 doi:10.1074/jbc.M809654200

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3fmz"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Retinol-Binding Protein 4 (RBP4) in complex with non-retinoid ligand==
 <StructureSection load='3fmz' size='340' side='right' caption='[[3fmz]], [[Resolution|resolution]] 2.90&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=2T1:2-[({4-[2-(TRIFLUOROMETHYL)PHENYL]PIPERIDIN-1-YL}CARBONYL)AMINO]BENZOIC+ACID'>2T1</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RBP4, PRO2222 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3fmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fmz OCA], [http://pdbe.org/3fmz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fmz RCSB], [http://www.ebi.ac.uk/pdbsum/3fmz 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=3fmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fmz OCA], [http://pdbe.org/3fmz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fmz RCSB], [http://www.ebi.ac.uk/pdbsum/3fmz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fmz ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fm/3fmz_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fm/3fmz_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

3fmz

From Proteopedia

Revision as of 07:56, 5 December 2018

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

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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