View source for 6ljx


==Crystal structure of human FABP4 in complex with a novel inhibitor==
<StructureSection load='6ljx' size='340' side='right'caption='[[6ljx]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ljx]] is a 1 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=6LJX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LJX 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=EHO:2-phenylazanylbenzoic+acid'>EHO</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=6ljx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ljx OCA], [https://pdbe.org/6ljx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ljx RCSB], [https://www.ebi.ac.uk/pdbsum/6ljx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ljx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FABP4_HUMAN FABP4_HUMAN] 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 (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Fatty-acid binding protein 4 (FABP4) is a promising therapeutic target for immunometabolic diseases, while its potential for systemic inflammatory response syndrome treatment has not been explored. Here, a series of 2-(phenylamino)benzoic acids as novel and potent FABP4 inhibitors are rationally designed based on an interesting fragment that adopts multiple binding poses within FABP4. A fusion of these binding poses leads to the design of compound 3 with an approximately 460-fold improvement in binding affinity compared to the initial fragment. A subsequent structure-aided optimization upon 3 results in a promising lead (17) with the highest binding affinity among all the inhibitors, exerting a significant anti-inflammatory effect in cells and effectively attenuating a systemic inflammatory damage in mice. Our work therefore presents a good example of lead compound discovery derived from the multiple binding poses of a fragment and provides a candidate for development of drugs against inflammation-related diseases.

Exploration of Fragment Binding Poses Leading to Efficient Discovery of Highly Potent and Orally Effective Inhibitors of FABP4 for Anti-inflammation.,Su H, Zou Y, Chen G, Dou H, Xie H, Yuan X, Zhang X, Zhang N, Li M, Xu Y J Med Chem. 2020 Apr 10. doi: 10.1021/acs.jmedchem.9b02107. PMID:32202425<ref>PMID:32202425</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ljx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Fatty acid-binding protein 3D structures|Fatty acid-binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Li MJ]]
[[Category: Su HX]]
[[Category: Xu YC]]
[[Category: Zhang XL]]