6qpl: Difference between revisions

From Proteopedia
Jump to navigationJump to search
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
New page: '''Unreleased structure''' The entry 6qpl is ON HOLD Authors: Johansson, C., Krojer, T., Xiong, Y., Jin, J., Arrowsmith, C.H., Bountra, C., Edwards, A., Oppermann, U.C.T. Description: ...
 
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
 
(4 intermediate revisions by the same user not shown)
Line 1: Line 1:
'''Unreleased structure'''


The entry 6qpl is ON HOLD
==Crystal structure of Spindlin1 in complex with the inhibitor MS31==
<StructureSection load='6qpl' size='340' side='right'caption='[[6qpl]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qpl]] 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=6QPL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QPL 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]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JC5:[3-(aminomethyl)-5-[3-(1,3-dihydroisoindol-2-yl)propoxy]-4-methoxy-phenyl]methanamine'>JC5</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6qpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qpl OCA], [https://pdbe.org/6qpl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qpl RCSB], [https://www.ebi.ac.uk/pdbsum/6qpl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qpl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPIN1_HUMAN SPIN1_HUMAN] May play a role in cell-cycle regulation during the transition from gamete to embryo (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
By screening an epigenetic compound library, we identified that UNC0638, a highly potent inhibitor of the histone methyltransferases G9a and GLP, was a weak inhibitor of SPIN1 (Spindlin 1), a methyllysine reader protein. Our optimization of this weak hit resulted in the discovery of a potent, selective and cell-active SPIN1 inhibitor, compound 3 (MS31). Compound 3 potently inhibited binding of trimethyllysine-containing peptides to SPIN1, displayed high binding affinity, was highly selective for SPIN1 over other epigenetic readers and writers, directly engaged SPIN1 in cells, and was not toxic to non-tumorigenic cells. The crystal structure of the SPIN1-compound 3 complex indicated that it selectively binds Tudor domain II of SPIN1. We also designed a structurally similar but inactive compound 4 (MS31N) as a negative control. Our results have demonstrated for the first time that potent, selective and cell-active fragment-like inhibitors can be generated by targeting a single Tudor domain.


Authors: Johansson, C., Krojer, T., Xiong, Y., Jin, J., Arrowsmith, C.H., Bountra, C., Edwards, A., Oppermann, U.C.T.
Discovery of a Potent and Selective Fragment-like Inhibitor of Methyllysine Reader Protein Spindlin 1 (SPIN1).,Xiong Y, Greschik H, Johansson C, Seifert L, Bacher J, Park KS, Babault N, Martini ML, Fagan V, Li F, Chau I, Christott T, Dilworth D, Barsyte-Lovejoy D, Vedadi M, Arrowsmith CH, Brennan PE, Fedorov O, Jung M, Farnie G, Liu J, Oppermann UCT, Schule R, Jin J J Med Chem. 2019 Jul 1. doi: 10.1021/acs.jmedchem.9b00522. PMID:31260300<ref>PMID:31260300</ref>


Description: Crystal structure of Spindlin1 in complex with the inhibitor MS31
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Arrowsmith, C.H]]
<div class="pdbe-citations 6qpl" style="background-color:#fffaf0;"></div>
[[Category: Xiong, Y]]
 
[[Category: Oppermann, U.C.T]]
==See Also==
[[Category: Johansson, C]]
*[[Spindlin|Spindlin]]
[[Category: Edwards, A]]
== References ==
[[Category: Krojer, T]]
<references/>
[[Category: Jin, J]]
__TOC__
[[Category: Bountra, C]]
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arrowsmith CH]]
[[Category: Bountra C]]
[[Category: Edwards A]]
[[Category: Jin J]]
[[Category: Johansson C]]
[[Category: Krojer T]]
[[Category: Oppermann UCT]]
[[Category: Xiong Y]]
Retrieved from "https://proteopedia.org/6qpl"