3o5f: Difference between revisions
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< | ==Fk1 domain of FKBP51, crystal form VII== | ||
<StructureSection load='3o5f' size='340' side='right'caption='[[3o5f]], [[Resolution|resolution]] 1.65Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3o5f]] 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=3O5F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O5F 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]] 1.65Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</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=3o5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o5f OCA], [https://pdbe.org/3o5f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o5f RCSB], [https://www.ebi.ac.uk/pdbsum/3o5f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o5f 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 == | |||
Steroid hormone receptors are key components of mammalian stress and sex hormone systems. Many of them rely on the Hsp90 chaperone system for full function and are further fine-tuned by Hsp90-associated peptidyl-prolyl isomerases such as FK506-binding proteins 51 and 52. FK506-binding protein 51 (FKBP51) has been shown to reduce glucocorticoid receptor signalling and has been genetically associated with human stress resilience and with numerous psychiatric disorders. The peptidyl-prolyl isomerase domain of FKBP51 contains a high-affinity binding site for the natural products FK506 and rapamycin and has further been shown to convey most of the inhibitory activity on the glucocorticoid receptor. FKBP51 has therefore become a prime new target for the treatment of stress-related affective disorders that could be amenable to structure-based drug design. Here, a series of high-resolution structures of the peptidyl-prolyl isomerase domain of FKBP51 as well as a cocrystal structure with the prototypic ligand FK506 are described. These structures provide a detailed picture of the drug-binding domain of FKBP51 and the molecular binding mode of its ligand as a starting point for the rational design of improved inhibitors. | |||
Structural characterization of the PPIase domain of FKBP51, a cochaperone of human Hsp90.,Bracher A, Kozany C, Thost AK, Hausch F Acta Crystallogr D Biol Crystallogr. 2011 Jun;67(Pt 6):549-59. Epub 2011 May 17. PMID:21636895<ref>PMID:21636895</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3o5f" style="background-color:#fffaf0;"></div> | |||
== | |||
==See Also== | ==See Also== | ||
*[[FKBP]] | *[[FKBP 3D structures|FKBP 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bracher | [[Category: Bracher A]] | ||
[[Category: Hausch | [[Category: Hausch F]] | ||
[[Category: Kozany | [[Category: Kozany C]] | ||
[[Category: Thost | [[Category: Thost A-K]] | ||
Latest revision as of 12:28, 6 September 2023
Fk1 domain of FKBP51, crystal form VIIFk1 domain of FKBP51, crystal form VII
Structural highlights
FunctionFKBP5_HUMAN Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP. Publication Abstract from PubMedSteroid hormone receptors are key components of mammalian stress and sex hormone systems. Many of them rely on the Hsp90 chaperone system for full function and are further fine-tuned by Hsp90-associated peptidyl-prolyl isomerases such as FK506-binding proteins 51 and 52. FK506-binding protein 51 (FKBP51) has been shown to reduce glucocorticoid receptor signalling and has been genetically associated with human stress resilience and with numerous psychiatric disorders. The peptidyl-prolyl isomerase domain of FKBP51 contains a high-affinity binding site for the natural products FK506 and rapamycin and has further been shown to convey most of the inhibitory activity on the glucocorticoid receptor. FKBP51 has therefore become a prime new target for the treatment of stress-related affective disorders that could be amenable to structure-based drug design. Here, a series of high-resolution structures of the peptidyl-prolyl isomerase domain of FKBP51 as well as a cocrystal structure with the prototypic ligand FK506 are described. These structures provide a detailed picture of the drug-binding domain of FKBP51 and the molecular binding mode of its ligand as a starting point for the rational design of improved inhibitors. Structural characterization of the PPIase domain of FKBP51, a cochaperone of human Hsp90.,Bracher A, Kozany C, Thost AK, Hausch F Acta Crystallogr D Biol Crystallogr. 2011 Jun;67(Pt 6):549-59. Epub 2011 May 17. PMID:21636895[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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