3smr

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<StructureSection load='3smr' size='340' side='right'caption='[[3smr]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
<StructureSection load='3smr' size='340' side='right'caption='[[3smr]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3smr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SMR FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3smr]] is a 4 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=3SMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SMR FirstGlance]. <br>
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</td></tr><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=NP7:2-CHLORO-N-[2-(4-METHYLPIPERAZIN-1-YL)-5-NITROPHENYL]BENZAMIDE'>NP7</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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]] 1.82&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WDR5, BIG3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=NP7:2-CHLORO-N-[2-(4-METHYLPIPERAZIN-1-YL)-5-NITROPHENYL]BENZAMIDE'>NP7</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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=3smr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3smr OCA], [https://pdbe.org/3smr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3smr RCSB], [https://www.ebi.ac.uk/pdbsum/3smr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3smr 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=3smr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3smr OCA], [https://pdbe.org/3smr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3smr RCSB], [https://www.ebi.ac.uk/pdbsum/3smr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3smr ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/WDR5_HUMAN WDR5_HUMAN]] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.<ref>PMID:19556245</ref> <ref>PMID:19103755</ref> <ref>PMID:20018852</ref> <ref>PMID:16600877</ref> <ref>PMID:16829960</ref>
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[https://www.uniprot.org/uniprot/WDR5_HUMAN WDR5_HUMAN] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.<ref>PMID:19556245</ref> <ref>PMID:19103755</ref> <ref>PMID:20018852</ref> <ref>PMID:16600877</ref> <ref>PMID:16829960</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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WDR5 (WD40 repeat protein 5) is an essential component of the human trithorax-like family of SET1 [Su(var)3-9 enhancer-of-zeste trithorax 1] methyltransferase complexes that carry out trimethylation of histone 3 Lys4 (H3K4me3), play key roles in development and are abnormally expressed in many cancers. In the present study, we show that the interaction between WDR5 and peptides from the catalytic domain of MLL (mixed-lineage leukaemia protein) (KMT2) can be antagonized with a small molecule. Structural and biophysical analysis show that this antagonist binds in the WDR5 peptide-binding pocket with a Kd of 450 nM and inhibits the catalytic activity of the MLL core complex in vitro. The degree of inhibition was enhanced at lower protein concentrations consistent with a role for WDR5 in directly stabilizing the MLL multiprotein complex. Our data demonstrate inhibition of an important protein-protein interaction and form the basis for further development of inhibitors of WDR5-dependent enzymes implicated in MLL-rearranged leukaemias or other cancers.
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Small-molecule inhibition of MLL activity by disruption of its interaction with WDR5.,Senisterra G, Wu H, Allali-Hassani A, Wasney GA, Barsyte-Lovejoy D, Dombrovski L, Dong A, Nguyen KT, Smil D, Bolshan Y, Hajian T, He H, Seitova A, Chau I, Li F, Poda G, Couture JF, Brown PJ, Al-Awar R, Schapira M, Arrowsmith CH, Vedadi M Biochem J. 2013 Jan 1;449(1):151-9. doi: 10.1042/BJ20121280. PMID:22989411<ref>PMID:22989411</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 3smr" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Al-Awar, R]]
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[[Category: Al-Awar R]]
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[[Category: Arrowsmith, C H]]
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[[Category: Arrowsmith CH]]
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[[Category: Bolshan, Y]]
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[[Category: Bolshan Y]]
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[[Category: Bountra, C]]
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[[Category: Bountra C]]
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[[Category: Brown, P J]]
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[[Category: Brown PJ]]
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[[Category: Dombrovski, L]]
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[[Category: Dombrovski L]]
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[[Category: Dong, A]]
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[[Category: Dong A]]
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[[Category: Edwards, A M]]
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[[Category: Edwards AM]]
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[[Category: Hajian, T]]
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[[Category: Hajian T]]
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[[Category: Nguyen, K T]]
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[[Category: Nguyen KT]]
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[[Category: Poda, G]]
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[[Category: Poda G]]
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[[Category: Structural genomic]]
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[[Category: Schapira M]]
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[[Category: Schapira, M]]
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[[Category: Senisterra G]]
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[[Category: Senisterra, G]]
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[[Category: Smil D]]
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[[Category: Smil, D]]
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[[Category: Tempel W]]
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[[Category: Tempel, W]]
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[[Category: Vedadi M]]
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[[Category: Vedadi, M]]
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[[Category: Wasney GA]]
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[[Category: Wasney, G A]]
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[[Category: Weigelt J]]
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[[Category: Weigelt, J]]
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[[Category: Wu H]]
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[[Category: Wu, H]]
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[[Category: Sgc]]
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[[Category: Transcription]]
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[[Category: Wd repeat domain 5]]
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[[Category: Wdr5]]
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Current revision

Crystal structure of human WD repeat domain 5 with compound

PDB ID 3smr

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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