7a6x: Difference between revisions
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<StructureSection load='7a6x' size='340' side='right'caption='[[7a6x]], [[Resolution|resolution]] 1.67Å' scene=''> | <StructureSection load='7a6x' size='340' side='right'caption='[[7a6x]], [[Resolution|resolution]] 1.67Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7a6x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <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='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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.67Å</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> | <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> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 7a6x" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7a6x" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[FKBP 3D structures|FKBP 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bauder M]] | |||
[[Category: Bauder | [[Category: Hausch F]] | ||
[[Category: Hausch | [[Category: Heymann T]] | ||
[[Category: Heymann | [[Category: Merz S]] | ||
[[Category: Merz | [[Category: Meyners C]] | ||
[[Category: Meyners | [[Category: Purder P]] | ||
[[Category: Purder | [[Category: Voll A]] | ||
[[Category: Voll | |||
Latest revision as of 15:04, 1 February 2024
Structure of the FKBP51FK1 domain in complex with the macrocyclic SAFit analogue 56Structure of the FKBP51FK1 domain in complex with the macrocyclic SAFit analogue 56
Structural highlights
FunctionFKBP5_HUMAN Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP. Publication Abstract from PubMedThe 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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