View source for 5diu


==The Fk1 domain of FKBP51 in complex with the new synthetic ligand 2-(3-((R)-1-((S)-1-((S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl)piperidine-2-carboxamido)-3-(3,4-dimethoxyphenyl)propyl)phenoxy)acetic acid==
<StructureSection load='5diu' size='340' side='right'caption='[[5diu]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5diu]] 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=5DIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DIU 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]] 1.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5BG:{3-[(1R)-1-[({(2S)-1-[(2S)-2-CYCLOHEXYL-2-(3,4,5-TRIMETHOXYPHENYL)ACETYL]PIPERIDIN-2-YL}CARBONYL)AMINO]-3-(3,4-DIMETHOXYPHENYL)PROPYL]PHENOXY}ACETIC+ACID'>5BG</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=5diu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5diu OCA], [https://pdbe.org/5diu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5diu RCSB], [https://www.ebi.ac.uk/pdbsum/5diu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5diu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FKBP5_HUMAN FKBP5_HUMAN] Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The FK506-binding protein 51 (FKBP51) is a key regulator of stress hormone receptors and an established risk factor for stress-related disorders. Drug development for FKBP51 has been impaired by the structurally similar but functionally opposing homologue FKBP52. High selectivity between FKBP51 and FKBP52 can be achieved by ligands that stabilize a recently discovered FKBP51-favoring conformation. However, drug-like parameters for these ligands remained unfavorable. In the present study, we replaced the potentially labile pipecolic ester group of previous FKBP51 ligands by various low molecular weight amides. This resulted in the first series of pipecolic acid amides, which had much lower molecular weights without affecting FKBP51 selectivity. We discovered a geminally substituted cyclopentyl amide as a preferred FKBP51-binding motif and elucidated its binding mode to provide a new lead structure for future drug optimization.

Rapid, Structure-Based Exploration of Pipecolic Acid Amides as Novel Selective Antagonists of the FK506-Binding Protein 51.,Gaali S, Feng X, Hahle A, Sippel C, Bracher A, Hausch F J Med Chem. 2016 Mar 24;59(6):2410-22. doi: 10.1021/acs.jmedchem.5b01355. Epub, 2016 Mar 8. PMID:26954324<ref>PMID:26954324</ref>

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

==See Also==
*[[FKBP 3D structures|FKBP 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bracher A]]
[[Category: Feng X]]
[[Category: Gaali S]]
[[Category: Hausch F]]
[[Category: Sippel C]]