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6t1i

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<StructureSection load='6t1i' size='340' side='right'caption='[[6t1i]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='6t1i' size='340' side='right'caption='[[6t1i]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6t1i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T1I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6T1I FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6t1i]] 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=6T1I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T1I FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=M7W:4-(4-ethanoylphenyl)-~{N}-[(6-methoxypyridin-3-yl)methyl]piperazine-1-carboxamide'>M7W</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<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=6t1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t1i OCA], [http://pdbe.org/6t1i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6t1i RCSB], [http://www.ebi.ac.uk/pdbsum/6t1i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6t1i ProSAT]</span></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=M7W:4-(4-ethanoylphenyl)-~{N}-[(6-methoxypyridin-3-yl)methyl]piperazine-1-carboxamide'>M7W</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6t1i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t1i OCA], [https://pdbe.org/6t1i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t1i RCSB], [https://www.ebi.ac.uk/pdbsum/6t1i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t1i ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/ENL_HUMAN ENL_HUMAN]] A chromosomal aberration involving MLLT1 is associated with acute leukemias. Translocation t(11;19)(q23;p13.3) with KMT2A/MLL1. The result is a rogue activator protein.
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[https://www.uniprot.org/uniprot/ENL_HUMAN ENL_HUMAN] A chromosomal aberration involving MLLT1 is associated with acute leukemias. Translocation t(11;19)(q23;p13.3) with KMT2A/MLL1. The result is a rogue activator protein.
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/ENL_HUMAN ENL_HUMAN]] Component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.<ref>PMID:20159561</ref> <ref>PMID:20471948</ref>
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[https://www.uniprot.org/uniprot/ENL_HUMAN ENL_HUMAN] Component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.<ref>PMID:20159561</ref> <ref>PMID:20471948</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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YEATS-domain-containing MLLT1 is an acetyl/acyl-lysine reader domain, which is structurally distinct from well-studied bromodomains and has been strongly associated in development of cancer. Here, we characterized piperazine-urea derivatives as an acetyl/acyl-lysine mimetic moiety for MLLT1. Crystal structures revealed distinct interaction mechanisms of this chemotype compared to the recently described benzimidazole-amide based inhibitors, exploiting different binding pockets within the protein. Thus, the piperazine-urea scaffold offers an alternative strategy for targeting the YEATS domain family.
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Structural Insights into Interaction Mechanisms of Alternative Piperazine-urea YEATS Domain Binders in MLLT1.,Ni X, Heidenreich D, Christott T, Bennett J, Moustakim M, Brennan PE, Fedorov O, Knapp S, Chaikuad A ACS Med Chem Lett. 2019 Nov 25;10(12):1661-1666. doi:, 10.1021/acsmedchemlett.9b00460. eCollection 2019 Dec 12. PMID:31857843<ref>PMID:31857843</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6t1i" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Arrowsmith, C H]]
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[[Category: Arrowsmith CH]]
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[[Category: Bountra, C]]
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[[Category: Bountra C]]
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[[Category: Chaikuad, A]]
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[[Category: Chaikuad A]]
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[[Category: Edwards, A M]]
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[[Category: Edwards AM]]
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[[Category: Fedorov, O]]
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[[Category: Fedorov O]]
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[[Category: Heidenreich, D]]
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[[Category: Heidenreich D]]
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[[Category: Knapp, S]]
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[[Category: Knapp S]]
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[[Category: Structural genomic]]
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[[Category: Chemical probe]]
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[[Category: Enl]]
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[[Category: Inhibitor]]
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[[Category: Mllt1]]
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[[Category: Sgc]]
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[[Category: Transcription]]
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[[Category: Yeats domain]]
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Current revision

Crystal structure of MLLT1 (ENL) YEATS domain in complexed with piperazine-urea derivative 1

PDB ID 6t1i

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