7ba0
From Proteopedia
(Difference between revisions)
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==Structure of the FKBP51FK1 domain in complex with the macrocyclic SAFit analogue 63== | ==Structure of the FKBP51FK1 domain in complex with the macrocyclic SAFit analogue 63== | ||
| - | <StructureSection load='7ba0' size='340' side='right'caption='[[7ba0]]' scene=''> | + | <StructureSection load='7ba0' size='340' side='right'caption='[[7ba0]], [[Resolution|resolution]] 1.14Å' 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=7BA0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BA0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7ba0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BA0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BA0 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=7ba0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ba0 OCA], [https://pdbe.org/7ba0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ba0 RCSB], [https://www.ebi.ac.uk/pdbsum/7ba0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ba0 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=T5H:2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-20,21-dihydroxy-25,28-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.2.2.113,17.04,9]nonacosa-1(26),13(29),14,16,24,27-hexaene-3,10-dione'>T5H</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FKBP5, AIG6, FKBP51 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </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=7ba0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ba0 OCA], [https://pdbe.org/7ba0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ba0 RCSB], [https://www.ebi.ac.uk/pdbsum/7ba0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ba0 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 7ba0" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Bauder M]] | + | [[Category: Peptidylprolyl isomerase]] |
| - | [[Category: Hausch F]] | + | [[Category: Bauder, M]] |
| - | [[Category: Heymann T]] | + | [[Category: Hausch, F]] |
| - | [[Category: Merz S]] | + | [[Category: Heymann, T]] |
| - | [[Category: Meyners C]] | + | [[Category: Merz, S]] |
| - | [[Category: Purder P]] | + | [[Category: Meyners, C]] |
| - | [[Category: Voll A]] | + | [[Category: Purder, P]] |
| + | [[Category: Voll, A]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Fkbp]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Isomerase]] | ||
| + | [[Category: Safit]] | ||
Revision as of 07:10, 7 April 2021
Structure of the FKBP51FK1 domain in complex with the macrocyclic SAFit analogue 63
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Categories: Human | Large Structures | Peptidylprolyl isomerase | Bauder, M | Hausch, F | Heymann, T | Merz, S | Meyners, C | Purder, P | Voll, A | Complex | Fkbp | Inhibitor | Isomerase | Safit
