3o5g: Difference between revisions
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[[ | ==Fk1 domain of FKBP51, crystal form I== | ||
<StructureSection load='3o5g' size='340' side='right' caption='[[3o5g]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3o5g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O5G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O5G FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3o5d|3o5d]], [[3o5e|3o5e]], [[3o5f|3o5f]], [[3o5i|3o5i]], [[3o5j|3o5j]], [[3o5k|3o5k]], [[3o5l|3o5l]], [[3o5m|3o5m]], [[3o5o|3o5o]], [[3o5p|3o5p]], [[3o5q|3o5q]], [[3o5r|3o5r]], [[1kt0|1kt0]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AIG6, FKBP5, FKBP51 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3o5g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o5g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o5g RCSB], [http://www.ebi.ac.uk/pdbsum/3o5g PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://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> | |||
==See Also== | ==See Also== | ||
*[[FK506 binding protein|FK506 binding protein]] | *[[FK506 binding protein|FK506 binding protein]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Peptidylprolyl isomerase]] | [[Category: Peptidylprolyl isomerase]] | ||
[[Category: Bracher, A | [[Category: Bracher, A]] | ||
[[Category: Hausch, F | [[Category: Hausch, F]] | ||
[[Category: Kozany, C | [[Category: Kozany, C]] | ||
[[Category: Thost, A K | [[Category: Thost, A K]] | ||
[[Category: Fk-506 binding domain]] | [[Category: Fk-506 binding domain]] | ||
[[Category: Hsp90 cochaperone]] | [[Category: Hsp90 cochaperone]] | ||
Revision as of 01:22, 25 December 2014
Fk1 domain of FKBP51, crystal form IFk1 domain of FKBP51, crystal form I
Structural highlights
Function[FKBP5_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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