View source for 6txx


==CRYSTAL STRUCTURE OF HUMAN FKBP51 FK1 DOMAIN A19T MUTANT IN COMPLEX WITH SAFit2==
<StructureSection load='6txx' size='340' side='right'caption='[[6txx]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6txx]] is a 2 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=6TXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TXX 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=37K:(1R)-3-(3,4-DIMETHOXYPHENYL)-1-{3-[2-(MORPHOLIN-4-YL)ETHOXY]PHENYL}PROPYL+(2S)-1-[(2S)-2-[(1S)-CYCLOHEX-2-EN-1-YL]-2-(3,4,5-TRIMETHOXYPHENYL)ACETYL]PIPERIDINE-2-CARBOXYLATE'>37K</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=6txx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6txx OCA], [https://pdbe.org/6txx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6txx RCSB], [https://www.ebi.ac.uk/pdbsum/6txx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6txx 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 ==
Fragment-based drug discovery (FBDD) deploys efficient sampling of the vast chemical space for hit identification. Libraries are screened biophysically and fragment:protein co-structures are determined by X-ray crystallography. In parallel, computational methods can derive pharmacophore models or screen virtual libraries. We screened 15 very small fragments (VSFs) (HA &lt;= 11) computationally, using site-identification by ligand competitive saturation (SILCS), and experimentally, by X-ray crystallography, to map potential interaction sites on the FKBP51 FK1 domain. We identified three hot spots and obtained 6 X-ray co-structures, giving a hit rate of 40%. SILCS FragMaps overlapped with X-ray structures. The compounds had millimolar affinities as determined by (15)N HSQC NMR. VSFs identified the same interactions as known FK1 binder and provide new chemical starting points. We propose a hybrid screening strategy starting with SILCS, followed by a pharmacophore-derived X-ray screen and (15)N HSQC NMR based KD determination to rapidly identify hits and their binding poses.

A hybrid screening approach for very small fragments - X-ray and Computational Screening on FKBP51.,Draxler SW, Bauer M, Eickmeier C, Nadal S, Nar H, Rangel D, Seeliger D, Zeeb M, Fiegen D J Med Chem. 2020 May 18. doi: 10.1021/acs.jmedchem.0c00120. PMID:32420743<ref>PMID:32420743</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6txx" style="background-color:#fffaf0;"></div>

==See Also==
*[[FKBP 3D structures|FKBP 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Draxler SW]]
[[Category: Fiegen D]]