6i8l
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6i8l is ON HOLD Authors: Johansson, C., Fagan, V., Brennan, P.E., Sorrell, F.J., Krojer, T., Arrowsmith, C.H., Bountra, C., Edwards, A., Oppermann, ...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Spindlin1 in complex with the inhibitor TD001851a== | |
| + | <StructureSection load='6i8l' size='340' side='right'caption='[[6i8l]], [[Resolution|resolution]] 1.58Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6i8l]] 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=6I8L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I8L 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]] 1.58Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=H7Q:5-(cyclopropylmethoxy)-6-[3-(1,3-dihydroisoindol-2-yl)propoxy]spiro[cyclopentane-1,3-indole]-2-amine'>H7Q</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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=6i8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i8l OCA], [https://pdbe.org/6i8l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i8l RCSB], [https://www.ebi.ac.uk/pdbsum/6i8l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i8l 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 == | ||
| + | Modifications of histone tails, including lysine/arginine methylation, provide the basis of a "chromatin or histone code". Proteins that contain "reader" domains can bind to these modifications and form specific effector complexes, which ultimately mediate chromatin function. The spindlin1 (SPIN1) protein contains three Tudor methyllysine/arginine reader domains and was identified as a putative oncogene and transcriptional coactivator. Here we report a SPIN1 chemical probe inhibitor with low nanomolar in vitro activity, exquisite selectivity on a panel of methyl reader and writer proteins, and with submicromolar cellular activity. X-ray crystallography showed that this Tudor domain chemical probe simultaneously engages Tudor domains 1 and 2 via a bidentate binding mode. Small molecule inhibition and siRNA knockdown of SPIN1, as well as chemoproteomic studies, identified genes which are transcriptionally regulated by SPIN1 in squamous cell carcinoma and suggest that SPIN1 may have a role in cancer related inflammation and/or cancer metastasis. | ||
| - | + | A Chemical Probe for Tudor Domain Protein Spindlin1 to Investigate Chromatin Function.,Fagan V, Johansson C, Gileadi C, Monteiro O, Dunford JE, Nibhani R, Philpott M, Malzahn J, Wells G, Faram R, Cribbs AP, Halidi N, Li F, Chau I, Greschik H, Velupillai S, Allali-Hassani A, Bennett J, Christott T, Giroud C, Lewis AM, Huber KVM, Athanasou N, Bountra C, Jung M, Schule R, Vedadi M, Arrowsmith C, Xiong Y, Jin J, Fedorov O, Farnie G, Brennan PE, Oppermann U J Med Chem. 2019 Oct 24;62(20):9008-9025. doi: 10.1021/acs.jmedchem.9b00562. Epub , 2019 Oct 15. PMID:31550156<ref>PMID:31550156</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[ | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6i8l" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Spindlin|Spindlin]] |
| - | [[Category: Brennan | + | == References == |
| - | [[Category: Edwards | + | <references/> |
| - | [[Category: Krojer | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: Sorrell | + | [[Category: Homo sapiens]] |
| + | [[Category: Large Structures]] | ||
| + | [[Category: Arrowsmith CH]] | ||
| + | [[Category: Bountra C]] | ||
| + | [[Category: Brennan PE]] | ||
| + | [[Category: Edwards A]] | ||
| + | [[Category: Fagan V]] | ||
| + | [[Category: Johansson C]] | ||
| + | [[Category: Krojer T]] | ||
| + | [[Category: Oppermann UCT]] | ||
| + | [[Category: Sorrell FJ]] | ||
Current revision
Crystal structure of Spindlin1 in complex with the inhibitor TD001851a
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Categories: Homo sapiens | Large Structures | Arrowsmith CH | Bountra C | Brennan PE | Edwards A | Fagan V | Johansson C | Krojer T | Oppermann UCT | Sorrell FJ
