4ia9
From Proteopedia
(Difference between revisions)
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== Function == | == Function == | ||
[[http://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> | [[http://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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The WD40-repeat protein WDR5 plays a critical role in maintaining the integrity of MLL complexes and fully activating their methyltransferase function. MLL complexes, the trithorax-like family of SET1 methyltransferases, catalyze trimethylation of lysine 4 on histone 3, and they have been widely implicated in various cancers. Antagonism of WDR5 and MLL subunit interaction by small molecules has recently been presented as a practical way to inhibit activity of the MLL1 complex, and N-(2-(4-methylpiperazin-1-yl)-5-substituted-phenyl) benzamides were reported as potent and selective antagonists of such an interaction. Here, we describe the protein crystal structure guided optimization of prototypic compound 2 (K dis = 7 muM), leading to identification of more potent antagonist 47 (K dis = 0.3 muM). | ||
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| + | Synthesis, Optimization, and Evaluation of Novel Small Molecules as Antagonists of WDR5-MLL Interaction.,Bolshan Y, Getlik M, Kuznetsova E, Wasney GA, Hajian T, Poda G, Nguyen KT, Wu H, Dombrovski L, Dong A, Senisterra G, Schapira M, Arrowsmith CH, Brown PJ, Al-Awar R, Vedadi M, Smil D ACS Med Chem Lett. 2013 Feb 4;4(3):353-7. doi: 10.1021/ml300467n. eCollection, 2013 Mar 14. PMID:24900672<ref>PMID:24900672</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4ia9" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
| - | *[[WD | + | *[[WD repeat-containing protein|WD repeat-containing protein]] |
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Wasney, G A]] | [[Category: Wasney, G A]] | ||
[[Category: Wu, H]] | [[Category: Wu, H]] | ||
| + | [[Category: Sgc]] | ||
[[Category: Transcription]] | [[Category: Transcription]] | ||
[[Category: Wd repeat domain 5]] | [[Category: Wd repeat domain 5]] | ||
[[Category: Wdr5]] | [[Category: Wdr5]] | ||
Revision as of 05:42, 16 May 2018
Crystal structure of human WD REPEAT DOMAIN 5 in complex with 2-chloro-4-fluoro-3-methyl-N-[2-(4-methylpiperazin-1-yl)-5-nitrophenyl]benzamide
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Categories: Human | Al-awar, R | Arrowsmith, C H | Bolshan, Y | Bountra, C | Brown, P J | Dombrovski, L | Dong, A | Edwards, A M | Getlik, M | Hajian, T | Kuznetsova, E | Nguyen, K T | Poda, G | Structural genomic | Schapira, M | Smil, D | Tempel, W | Vedadi, M | Wasney, G A | Wu, H | Sgc | Transcription | Wd repeat domain 5 | Wdr5
