8cca: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[8cca]] 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=8CCA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CCA FirstGlance]. <br>
<table><tr><td colspan='2'>[[8cca]] 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=8CCA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CCA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GY1:2-[3-[(1~{R})-1-[(2~{S})-1-[(2~{S})-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)ethanoyl]piperidin-2-yl]carbonyloxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]ethanoic+acid'>GY1</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]] 1.33&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GY1:2-[3-[(1~{R})-1-[(2~{S})-1-[(2~{S})-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)ethanoyl]piperidin-2-yl]carbonyloxy-3-(3,4-dimethoxyphenyl)propyl]phenoxy]ethanoic+acid'>GY1</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=8cca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cca OCA], [https://pdbe.org/8cca PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cca RCSB], [https://www.ebi.ac.uk/pdbsum/8cca PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cca 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=8cca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cca OCA], [https://pdbe.org/8cca PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cca RCSB], [https://www.ebi.ac.uk/pdbsum/8cca PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cca ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/FKBP5_HUMAN FKBP5_HUMAN] Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP.
[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 ==
In recent years, the selective inhibition of FKBP51 has emerged as a possible treatment for chronic pain, obesity-induced diabetes, or depression. All currently known advanced FKBP51-selective inhibitors, including the widely used SAFit2, contain a cyclohexyl residue as a key motif for enabling selectivity over the closest homologue and anti-target FKBP52. During a structure-based SAR exploration, we surprisingly discovered thiophenes as highly efficient cyclohexyl replacement moieties that retain the strong selectivity of SAFit-type inhibitors for FKBP51 over FKBP52. Cocrystal structures revealed that the thiophene-containing moieties enable selectivity by stabilizing a flipped-out conformation of Phe(67) of FKBP51. Our best compound, 19b, potently binds to FKBP51 biochemically as well as in mammalian cells, desensitize TRPV1 in primary sensory neurons, and has an acceptable PK profile in mice, suggesting its use as a novel tool compound for studying FKBP51 in animal models of neuropathic pain.
Structure-Based Discovery of a New Selectivity-Enabling Motif for the FK506-Binding Protein 51.,Knaup FH, Meyners C, Sugiarto WO, Wedel S, Springer M, Walz C, Geiger TM, Schmidt M, Sisignano M, Hausch F J Med Chem. 2023 Apr 14. doi: 10.1021/acs.jmedchem.3c00249. PMID:37058391<ref>PMID:37058391</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8cca" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Latest revision as of 06:30, 19 June 2024

The Fk1 domain of FKBP51 in complex with SAFit1

8cca, resolution 1.33Å

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