7awx
From Proteopedia
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==Structure of the FKBP51FK1 domain in complex with the macrocyclic SAFit analogue 55== | ==Structure of the FKBP51FK1 domain in complex with the macrocyclic SAFit analogue 55== | ||
| - | <StructureSection load='7awx' size='340' side='right'caption='[[7awx]]' scene=''> | + | <StructureSection load='7awx' size='340' side='right'caption='[[7awx]], [[Resolution|resolution]] 2.20Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AWX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7awx]] is a 2 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=7AWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AWX FirstGlance]. <br> |
| - | </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=7awx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7awx OCA], [https://pdbe.org/7awx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7awx RCSB], [https://www.ebi.ac.uk/pdbsum/7awx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7awx ProSAT]</span></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]] 2.2Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=S5W:Macrocyclic+SAFit+analogue+55'>S5W</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=7awx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7awx OCA], [https://pdbe.org/7awx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7awx RCSB], [https://www.ebi.ac.uk/pdbsum/7awx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7awx ProSAT]</span></td></tr> | ||
</table> | </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. | ||
| + | |||
| + | 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> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7awx" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[FKBP 3D structures|FKBP 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bauder M]] | [[Category: Bauder M]] | ||
Current revision
Structure of the FKBP51FK1 domain in complex with the macrocyclic SAFit analogue 55
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Categories: Homo sapiens | Large Structures | Bauder M | Hausch F | Heymann T | Merz S | Meyners C | Purder P | Voll A
