3fmz
From Proteopedia
(Difference between revisions)
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| - | + | ==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]] 2.90Å' scene=''> | |
| - | { | + | == Structural highlights == |
| - | + | <table><tr><td colspan='2'>[[3fmz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FMZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FMZ FirstGlance]. <br> | |
| - | ==Disease== | + | </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 Homo sapiens])</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://www.rcsb.org/pdb/explore.do?structureId=3fmz RCSB], [http://www.ebi.ac.uk/pdbsum/3fmz PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
[[http://www.uniprot.org/uniprot/RET4_HUMAN RET4_HUMAN]] Defects in RBP4 are a cause of retinol-binding protein deficiency (RBP deficiency) [MIM:[http://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. | [[http://www.uniprot.org/uniprot/RET4_HUMAN RET4_HUMAN]] Defects in RBP4 are a cause of retinol-binding protein deficiency (RBP deficiency) [MIM:[http://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 == | |
| - | ==Function== | + | |
[[http://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. | [[http://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. | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <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> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:19147488</ref> | |
| - | + | ||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
==See Also== | ==See Also== | ||
*[[Retinol-binding protein|Retinol-binding protein]] | *[[Retinol-binding protein|Retinol-binding protein]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Johnstone, S | + | [[Category: Johnstone, S]] |
| - | [[Category: Walker, N P | + | [[Category: Walker, N P]] |
| - | [[Category: Wang, Z | + | [[Category: Wang, Z]] |
[[Category: Disease mutation]] | [[Category: Disease mutation]] | ||
[[Category: Retinol binding]] | [[Category: Retinol binding]] | ||
Revision as of 14:09, 18 December 2014
Crystal Structure of Retinol-Binding Protein 4 (RBP4) in complex with non-retinoid ligand
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