View source for 5hzq


==Crystal structure of cellular retinoic acid binding protein 2 (CRABP2)-aryl fluorosulfate covalent conjugate==
<StructureSection load='5hzq' size='340' side='right'caption='[[5hzq]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5hzq]] 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=5HZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HZQ 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]] 1.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=YWZ:4-[(3,6,9,12-TETRAOXAPENTADEC-14-YN-1-YL)OXY][1,1-BIPHENYL]-4-YL+SULFUROFLUORIDATE'>YWZ</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=5hzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hzq OCA], [https://pdbe.org/5hzq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hzq RCSB], [https://www.ebi.ac.uk/pdbsum/5hzq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hzq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RABP2_HUMAN RABP2_HUMAN] Transports retinoic acid to the nucleus. Regulates the access of retinoic acid to the nuclear retinoic acid receptors.
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== Publication Abstract from PubMed ==
Arylfluorosulfates have appeared only rarely in the literature and have not been explored as probes for covalent conjugation to proteins, possibly because they were assumed to possess high reactivity, as with other sulfur(VI) halides. However, we find that arylfluorosulfates become reactive only under certain circumstances, e.g., when fluoride displacement by a nucleophile is facilitated. Herein, we explore the reactivity of structurally simple arylfluorosulfates towards the proteome of human cells. We demonstrate that the protein reactivity of arylfluorosulfates is lower than that of the corresponding aryl sulfonyl fluorides, which are better characterized with regard to proteome reactivity. We discovered that simple hydrophobic arylfluorosulfates selectively react with a few members of the intracellular lipid binding protein (iLBP) family. A central function of iLBPs is to deliver small-molecule ligands to nuclear hormone receptors. Arylfluorosulfate probe 1 reacts with a conserved tyrosine residue in the ligand-binding site of a subset of iLBPs. Arylfluorosulfate probes 3 and 4, featuring a biphenyl core, very selectively and efficiently modify cellular retinoic acid binding protein 2 (CRABP2), both in vitro and in living cells. The x-ray crystal structure of the CRABP2-4 conjugate, when considered together with binding site mutagenesis experiments, provides insight into how CRABP2 might activate arylfluorosulfates toward site-specific reaction. Treatment of breast cancer cells with probe 4 attenuates nuclear hormone receptor activity mediated by retinoic acid, an endogenous client lipid of CRABP2. Our findings demonstrate that arylfluorosulfates can selectively target single iLBPs, making them useful for understanding iLBP function.

Arylfluorosulfates Inactivate Intracellular Lipid Binding Protein(s) through Chemoselective SuFEx Reaction with a Binding-site Tyr Residue.,Chen W, Dong J, Plate L, Mortenson DE, Brighty GJ, Li S, Liu Y, Galmozzi A, Lee PS, Hulce JJ, Cravatt BF, Saez E, Powers ET, Wilson IA, Sharpless KB, Kelly JW J Am Chem Soc. 2016 May 18. PMID:27191344<ref>PMID:27191344</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5hzq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cellular retinoic acid-binding protein 3D structures|Cellular retinoic acid-binding protein 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen W]]
[[Category: Kelly JW]]
[[Category: Mortenson DE]]
[[Category: Wilson IA]]