6cko: Difference between revisions

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 ==Crystal structure of an AF10 fragment==
-<StructureSection load='6cko' size='340' side='right' caption='[[6cko]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='6cko' size='340' side='right'caption='[[6cko]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6cko]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CKO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CKO FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6cko]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CKO FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6cko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cko OCA], [http://pdbe.org/6cko PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cko RCSB], [http://www.ebi.ac.uk/pdbsum/6cko PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cko ProSAT]</span></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=6cko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cko OCA], [https://pdbe.org/6cko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cko RCSB], [https://www.ebi.ac.uk/pdbsum/6cko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cko ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/AF10_HUMAN AF10_HUMAN]] Precursor T-cell acute lymphoblastic leukemia. A chromosomal aberration involving MLLT10 is associated with acute leukemias. Translocation t(10;11)(p12;q23) with KMT2A/MLL1. The result is a rogue activator protein.  A chromosomal aberration involving MLLT10 is associated with diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with PICALM.
+[https://www.uniprot.org/uniprot/AF10_HUMAN AF10_HUMAN] Precursor T-cell acute lymphoblastic leukemia. A chromosomal aberration involving MLLT10 is associated with acute leukemias. Translocation t(10;11)(p12;q23) with KMT2A/MLL1. The result is a rogue activator protein.  A chromosomal aberration involving MLLT10 is associated with diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with PICALM.
 == Function ==
-[[http://www.uniprot.org/uniprot/AF10_HUMAN AF10_HUMAN]] Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA.<ref>PMID:17868029</ref>
+[https://www.uniprot.org/uniprot/AF10_HUMAN AF10_HUMAN] Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA.<ref>PMID:17868029</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The mixed-lineage leukemia (MLL)-AF10 fusion oncoprotein recruits DOT1L to the homeobox A (HOXA) gene cluster through its octapeptide motif leucine zipper (OM-LZ), thereby inducing and maintaining the MLL-AF10-associated leukemogenesis. However, the recognition mechanism between DOT1L and MLL-AF10 is unclear. Here, we present the crystal structures of both apo AF10(OM-LZ) and its complex with the coiled-coil domain of DOT1L. Disruption of the DOT1L-AF10 interface abrogates MLL-AF10-associated leukemic transformation. We further show that zinc stabilizes the DOT1L-AF10 complex and may be involved in the regulation of the HOXA gene expression. Our studies may also pave the way for the rational design of therapeutic drugs against MLL-rearranged leukemia.
+Structural and functional analysis of the DOT1L-AF10 complex reveals mechanistic insights into MLL-AF10-associated leukemogenesis.,Zhang H, Zhou B, Qin S, Xu J, Harding R, Tempel W, Nayak V, Li Y, Loppnau P, Dou Y, Min J Genes Dev. 2018 Mar 1;32(5-6):341-346. doi: 10.1101/gad.311639.118. Epub 2018 Mar, 21. PMID:29563185<ref>PMID:29563185</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6cko" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Histone-lysine N-methyltransferase]]
+[[Category: Danio rerio]]
-[[Category: Arrowsmith, C H]]
+[[Category: Homo sapiens]]
-[[Category: Bountra, C]]
+[[Category: Large Structures]]
-[[Category: Edwards, A M]]
+[[Category: Arrowsmith CH]]
-[[Category: Min, J]]
+[[Category: Bountra C]]
-[[Category: Structural genomic]]
+[[Category: Edwards AM]]
-[[Category: Tempel, W]]
+[[Category: Min J]]
-[[Category: Zhang, H]]
+[[Category: Tempel W]]
-[[Category: Dna binding protein-transferase complex]]
+[[Category: Zhang H]]
-[[Category: Sgc]]