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< | ==Identification and Characterization of a Small Molecule Inhibitor of Fatty Acid Binding Proteins== | ||
<StructureSection load='3hk1' size='340' side='right'caption='[[3hk1]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3hk1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HK1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HK1 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]] 1.7Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B64:4-{[2-(METHOXYCARBONYL)-5-(2-THIENYL)-3-THIENYL]AMINO}-4-OXO-2-BUTENOIC+ACID'>B64</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=3hk1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hk1 OCA], [https://pdbe.org/3hk1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hk1 RCSB], [https://www.ebi.ac.uk/pdbsum/3hk1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hk1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FABP4_MOUSE FABP4_MOUSE] Lipid transport protein in adipocytes. Binds both long chain fatty acids and retinoic acid. Delivers long-chain fatty acids and retinoic acid to their cognate receptors in the nucleus.<ref>PMID:12077340</ref> <ref>PMID:16574478</ref> <ref>PMID:17516629</ref> | |||
== 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/hk/3hk1_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/main_output.php?pdb_ID=3hk1 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Molecular disruption of the lipid carrier AFABP/aP2 in mice results in improved insulin sensitivity and protection from atherosclerosis. Because small molecule inhibitors may be efficacious in defining the mechanism(s) of AFABP/aP2 action, a chemical library was screened and identified 1 (HTS01037) as a pharmacologic ligand capable of displacing the fluorophore 1-anilinonaphthalene 8-sulfonic acid from the lipid binding cavity. The X-ray crystal structure of 1 bound to AFABP/aP2 revealed that the ligand binds at a structurally similar position to a long-chain fatty acid. Similar to AFABP/aP2 knockout mice, 1 inhibits lipolysis in 3T3-L1 adipocytes and reduces LPS-stimulated inflammation in cultured macrophages. 1 acts as an antagonist of the protein-protein interaction between AFABP/aP2 and hormone sensitive lipase but does not activate PPARgamma in macrophage or CV-1 cells. These results identify 1 as an inhibitor of fatty acid binding and a competitive antagonist of protein-protein interactions mediated by AFABP/aP2. | |||
Identification and Characterization of a Small Molecule Inhibitor of Fatty Acid Binding Proteins.,Hertzel AV, Hellberg K, Reynolds JM, Kruse AC, Juhlmann BE, Smith AJ, Sanders MA, Ohlendorf DH, Suttles J, Bernlohr DA J Med Chem. 2009 Sep 16. PMID:19754198<ref>PMID:19754198</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3hk1" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Fatty acid-binding protein 3D structures|Fatty acid-binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
< | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Bernlohr | [[Category: Bernlohr DA]] | ||
[[Category: Hellberg | [[Category: Hellberg K]] | ||
[[Category: Hertzel | [[Category: Hertzel AV]] | ||
[[Category: Juhlmann | [[Category: Juhlmann BE]] | ||
[[Category: Kruse | [[Category: Kruse AC]] | ||
[[Category: Ohlendorf | [[Category: Ohlendorf DH]] | ||
[[Category: Reynolds | [[Category: Reynolds JM]] | ||
[[Category: Sanders | [[Category: Sanders MA]] | ||
[[Category: Smith | [[Category: Smith AJ]] | ||
[[Category: Suttles | [[Category: Suttles J]] | ||
Latest revision as of 10:23, 6 September 2023
Identification and Characterization of a Small Molecule Inhibitor of Fatty Acid Binding ProteinsIdentification and Characterization of a Small Molecule Inhibitor of Fatty Acid Binding Proteins
Structural highlights
FunctionFABP4_MOUSE Lipid transport protein in adipocytes. Binds both long chain fatty acids and retinoic acid. Delivers long-chain fatty acids and retinoic acid to their cognate receptors in the nucleus.[1] [2] [3] 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 PubMedMolecular disruption of the lipid carrier AFABP/aP2 in mice results in improved insulin sensitivity and protection from atherosclerosis. Because small molecule inhibitors may be efficacious in defining the mechanism(s) of AFABP/aP2 action, a chemical library was screened and identified 1 (HTS01037) as a pharmacologic ligand capable of displacing the fluorophore 1-anilinonaphthalene 8-sulfonic acid from the lipid binding cavity. The X-ray crystal structure of 1 bound to AFABP/aP2 revealed that the ligand binds at a structurally similar position to a long-chain fatty acid. Similar to AFABP/aP2 knockout mice, 1 inhibits lipolysis in 3T3-L1 adipocytes and reduces LPS-stimulated inflammation in cultured macrophages. 1 acts as an antagonist of the protein-protein interaction between AFABP/aP2 and hormone sensitive lipase but does not activate PPARgamma in macrophage or CV-1 cells. These results identify 1 as an inhibitor of fatty acid binding and a competitive antagonist of protein-protein interactions mediated by AFABP/aP2. Identification and Characterization of a Small Molecule Inhibitor of Fatty Acid Binding Proteins.,Hertzel AV, Hellberg K, Reynolds JM, Kruse AC, Juhlmann BE, Smith AJ, Sanders MA, Ohlendorf DH, Suttles J, Bernlohr DA J Med Chem. 2009 Sep 16. PMID:19754198[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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