6qpl: Difference between revisions

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'''Unreleased structure'''


The entry 6qpl is ON HOLD  until Paper Publication
==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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QPL FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6qpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qpl OCA], [http://pdbe.org/6qpl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qpl RCSB], [http://www.ebi.ac.uk/pdbsum/6qpl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qpl ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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]]
== References ==
[[Category: Oppermann, U.C.T]]
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Arrowsmith, C H]]
[[Category: Bountra, C]]
[[Category: Edwards, A]]
[[Category: Jin, J]]
[[Category: Johansson, C]]
[[Category: Johansson, C]]
[[Category: Edwards, A]]
[[Category: Krojer, T]]
[[Category: Krojer, T]]
[[Category: Jin, J]]
[[Category: Oppermann, U C.T]]
[[Category: Bountra, C]]
[[Category: Xiong, Y]]
[[Category: Cell cycle]]
[[Category: Epigenetic]]
[[Category: Methyl-arginine]]
[[Category: Methyl-lysine]]
[[Category: Tudor domain]]
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