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3hk1

From Proteopedia

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Current revision

Identification and Characterization of a Small Molecule Inhibitor of Fatty Acid Binding Proteins

Structural highlights

3hk1 is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[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 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^[4]

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

References

↑ Tan NS, Shaw NS, Vinckenbosch N, Liu P, Yasmin R, Desvergne B, Wahli W, Noy N. Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription. Mol Cell Biol. 2002 Jul;22(14):5114-27. PMID:12077340
↑ Adida A, Spener F. Adipocyte-type fatty acid-binding protein as inter-compartmental shuttle for peroxisome proliferator activated receptor gamma agonists in cultured cell. Biochim Biophys Acta. 2006 Feb;1761(2):172-81. Epub 2006 Mar 9. PMID:16574478 doi:http://dx.doi.org/S1388-1981(06)00031-X
↑ Ayers SD, Nedrow KL, Gillilan RE, Noy N. Continuous nucleocytoplasmic shuttling underlies transcriptional activation of PPARgamma by FABP4. Biochemistry. 2007 Jun 12;46(23):6744-52. Epub 2007 May 22. PMID:17516629 doi:http://dx.doi.org/10.1021/bi700047a
↑ Hertzel AV, Hellberg K, Reynolds JM, Kruse AC, Juhlmann BE, Smith AJ, Sanders MA, Ohlendorf DH, Suttles J, Bernlohr DA. Identification and Characterization of a Small Molecule Inhibitor of Fatty Acid Binding Proteins. J Med Chem. 2009 Sep 16. PMID:19754198 doi:10.1021/jm900720m

1 Structural highlights
2 Function
3 Evolutionary Conservation
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/3hk1"

@@ Line 3: / Line 3: @@
 <StructureSection load='3hk1' size='340' side='right'caption='[[3hk1]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3hk1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. 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>
+<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='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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">adipocyte, Ap2, Fabp4, fatty acid binding protein 4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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>
+[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]]
@@ Line 37: / Line 37: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
-[[Category: Bernlohr, D A]]
+[[Category: Bernlohr DA]]
-[[Category: Hellberg, K]]
+[[Category: Hellberg K]]
-[[Category: Hertzel, A V]]
+[[Category: Hertzel AV]]
-[[Category: Juhlmann, B E]]
+[[Category: Juhlmann BE]]
-[[Category: Kruse, A C]]
+[[Category: Kruse AC]]
-[[Category: Ohlendorf, D H]]
+[[Category: Ohlendorf DH]]
-[[Category: Reynolds, J M]]
+[[Category: Reynolds JM]]
-[[Category: Sanders, M A]]
+[[Category: Sanders MA]]
-[[Category: Smith, A J]]
+[[Category: Smith AJ]]
-[[Category: Suttles, J]]
+[[Category: Suttles J]]
-[[Category: Cytoplasm]]
-[[Category: Fatty acid binding protein]]
-[[Category: Lipid binding protein]]
-[[Category: Lipid-binding]]
-[[Category: Nucleus]]
-[[Category: Phosphoprotein]]
-[[Category: Protein binding]]
-[[Category: Transport]]

3hk1

From Proteopedia

Current revision

Identification and Characterization of a Small Molecule Inhibitor of Fatty Acid Binding Proteins

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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