4tw6: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4tw6]] 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=4TW6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TW6 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4tw6]] 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=4TW6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TW6 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=37L:(3-{(1R)-3-(3,4-DIMETHOXYPHENYL)-1-[({(2S)-1-[(2S)-2-(3,4,5-TRIMETHOXYPHENYL)PENT-4-ENOYL]PIPERIDIN-2-YL}CARBONYL)OXY]PROPYL}PHENOXY)ACETIC+ACID'>37L</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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]] 1.4Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=37L:(3-{(1R)-3-(3,4-DIMETHOXYPHENYL)-1-[({(2S)-1-[(2S)-2-(3,4,5-TRIMETHOXYPHENYL)PENT-4-ENOYL]PIPERIDIN-2-YL}CARBONYL)OXY]PROPYL}PHENOXY)ACETIC+ACID'>37L</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4tw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tw6 OCA], [https://pdbe.org/4tw6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tw6 RCSB], [https://www.ebi.ac.uk/pdbsum/4tw6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tw6 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=4tw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tw6 OCA], [https://pdbe.org/4tw6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tw6 RCSB], [https://www.ebi.ac.uk/pdbsum/4tw6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tw6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 15:25, 20 December 2023
The Fk1 domain of FKBP51 in complex with iFit1The Fk1 domain of FKBP51 in complex with iFit1
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, encoded by the FKBP5 gene) is an established risk factor for stress-related psychiatric disorders such as major depression. Drug discovery for FKBP51 has been hampered by the inability to pharmacologically differentiate against the structurally similar but functional opposing homolog FKBP52, and all known FKBP ligands are unselective. Here, we report the discovery of the potent and highly selective inhibitors of FKBP51, SAFit1 and SAFit2. This new class of ligands achieves selectivity for FKBP51 by an induced-fit mechanism that is much less favorable for FKBP52. By using these ligands, we demonstrate that selective inhibition of FKBP51 enhances neurite elongation in neuronal cultures and improves neuroendocrine feedback and stress-coping behavior in mice. Our findings provide the structural and functional basis for the development of mechanistically new antidepressants. Selective inhibitors of the FK506-binding protein 51 by induced fit.,Gaali S, Kirschner A, Cuboni S, Hartmann J, Kozany C, Balsevich G, Namendorf C, Fernandez-Vizarra P, Sippel C, Zannas AS, Draenert R, Binder EB, Almeida OF, Ruhter G, Uhr M, Schmidt MV, Touma C, Bracher A, Hausch F Nat Chem Biol. 2014 Dec 1. doi: 10.1038/nchembio.1699. PMID:25436518[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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