6ten
From Proteopedia
(Difference between revisions)
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<StructureSection load='6ten' size='340' side='right'caption='[[6ten]], [[Resolution|resolution]] 2.21Å' scene=''> | <StructureSection load='6ten' size='340' side='right'caption='[[6ten]], [[Resolution|resolution]] 2.21Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6ten]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TEN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6TEN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ten]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TEN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6TEN FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=N5K:3-[(4-azanyl-6-methoxy-1,3,5-triazin-2-yl)amino]-4-[[(~{S})-[2,2-bis(fluoranyl)-1,3-benzodioxol-4-yl]-(3-chloranylpyridin-2-yl)methyl]amino]benzenesulfonamide'>N5K</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=N5K:3-[(4-azanyl-6-methoxy-1,3,5-triazin-2-yl)amino]-4-[[(~{S})-[2,2-bis(fluoranyl)-1,3-benzodioxol-4-yl]-(3-chloranylpyridin-2-yl)methyl]amino]benzenesulfonamide'>N5K</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6te6|6te6]], [[6tel|6tel]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6te6|6te6]], [[6tel|6tel]]</td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/DOT1L_HUMAN DOT1L_HUMAN]] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA. | [[http://www.uniprot.org/uniprot/DOT1L_HUMAN DOT1L_HUMAN]] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In MLL-rearranged cancer cells, disruptor of telomeric silencing 1-like protein (DOT1L) is aberrantly recruited to ectopic loci leading to local hypermethylation of H3K79 and consequently misexpression of leukemogenic genes. A structure-guided optimization of a HTS hit led to the discovery of DOT1L inhibitors with subnanomolar potency, allowing testing of the therapeutic principle of DOT1L inhibition in a preclinical mouse tumor xenograft model. Compounds displaying good exposure in mouse and nanomolar inhibition of target gene expression in cells were obtained and tested in vivo. | ||
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| + | New Potent DOT1L Inhibitors for in Vivo Evaluation in Mouse.,Stauffer F, Weiss A, Scheufler C, Mobitz H, Ragot C, Beyer KS, Calkins K, Guthy D, Kiffe M, Van Eerdenbrugh B, Tiedt R, Gaul C ACS Med Chem Lett. 2019 Dec 4;10(12):1655-1660. doi:, 10.1021/acsmedchemlett.9b00452. eCollection 2019 Dec 12. PMID:31857842<ref>PMID:31857842</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6ten" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Histone-lysine N-methyltransferase]] | [[Category: Histone-lysine N-methyltransferase]] | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Be, C]] | [[Category: Be, C]] | ||
Revision as of 12:17, 1 January 2020
Crystal structure of Dot1L in complex with an inhibitor (compound 11).
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