7a6x: Difference between revisions

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-'''Unreleased structure'''
-The entry 7a6x is ON HOLD
+==Structure of the FKBP51FK1 domain in complex with the macrocyclic SAFit analogue 56==
+<StructureSection load='7a6x' size='340' side='right'caption='[[7a6x]], [[Resolution|resolution]] 1.67&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7a6x]] 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=7A6X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A6X 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]] 1.67&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=R3B:(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-24,27-dimethoxy-11,18,22-trioxa-4-azatetracyclo[21.2.2.113,17.04,9]octacosa-1(25),13(28),14,16,23,26-hexaene-3,10-dione'>R3B</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=7a6x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a6x OCA], [https://pdbe.org/7a6x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a6x RCSB], [https://www.ebi.ac.uk/pdbsum/7a6x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a6x 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) emerged as a key player in several diseases like stress-related disorders, chronic pain, and obesity. Linear analogues of FK506 called SAFit were shown to be highly selective for FKBP51 over its closest homologue FKBP52, allowing the proof-of-concept studies in animal models. Here, we designed and synthesized the first macrocyclic FKBP51-selective ligands to stabilize the active conformation. All macrocycles retained full FKBP51 affinity and selectivity over FKBP52 and the incorporation of polar functionalities further enhanced affinity. Six high-resolution crystal structures of macrocyclic inhibitors in complex with FKBP51 confirmed the desired selectivity-enabling binding mode. Our results show that macrocyclization is a viable strategy to target the shallow FKBP51 binding site selectively.
-Authors:
+Structure-Based Design of High-Affinity Macrocyclic FKBP51 Inhibitors.,Bauder M, Meyners C, Purder PL, Merz S, Sugiarto WO, Voll AM, Heymann T, Hausch F J Med Chem. 2021 Mar 5. doi: 10.1021/acs.jmedchem.0c02195. PMID:33666419<ref>PMID:33666419</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 7a6x" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[FKBP 3D structures|FKBP 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bauder M]]
+[[Category: Hausch F]]
+[[Category: Heymann T]]
+[[Category: Merz S]]
+[[Category: Meyners C]]
+[[Category: Purder P]]
+[[Category: Voll A]]