View source for 7axs


==Structural characterisation of WDR5:CS-VIP8 interaction in cis state 1==
<StructureSection load='7axs' size='340' side='right'caption='[[7axs]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7axs]] is a 2 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=7AXS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AXS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.88&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4FO:(2R)-2,4-DIAMINOBUTANOIC+ACID'>4FO</scene>, <scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=ALQ:2-METHYL-PROPIONIC+ACID'>ALQ</scene>, <scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=EDN:ETHANE-1,2-DIAMINE'>EDN</scene>, <scene name='pdbligand=S7Z:(E)-(4-((2,6-difluoro-4-(hydroxymethyl)phenyl)diazenyl)-2,6-difluorophenyl)methanol'>S7Z</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=7axs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7axs OCA], [https://pdbe.org/7axs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7axs RCSB], [https://www.ebi.ac.uk/pdbsum/7axs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7axs ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Optical control has enabled functional modulation in cell culture with unparalleled spatiotemporal resolution. However, current tools for in vivo manipulation are scarce. Here, we design and implement a genuine on-off optochemical probe capable of achieving hematopoietic control in zebrafish. Our photopharmacological approach first developed conformationally strained visible light photoswitches (CS-VIPs) as inhibitors of the histone methyltransferase MLL1 (KMT2A). In blood homeostasis MLL1 plays a crucial yet controversial role. CS-VIP 8 optimally fulfils the requirements of a true bistable functional system in vivo under visible-light irradiation, and with unprecedented stability. These properties are exemplified via hematopoiesis photoinhibition with a single isomer in zebrafish. The present interdisciplinary study uncovers the mechanism of action of CS-VIPs. Upon WDR5 binding, CS-VIP 8 causes MLL1 release with concomitant allosteric rearrangements in the WDR5/RbBP5 interface. Since our tool provides on-demand reversible control without genetic intervention or continuous irradiation, it will foster hematopathology and epigenetic investigations. Furthermore, our workflow will enable exquisite photocontrol over other targets inhibited by macrocycles.

Bistable Photoswitch Allows in Vivo Control of Hematopoiesis.,Albert L, Nagpal J, Steinchen W, Zhang L, Werel L, Djokovic N, Ruzic D, Hoffarth M, Xu J, Kaspareit J, Abendroth F, Royant A, Bange G, Nikolic K, Ryu S, Dou Y, Essen LO, Vazquez O ACS Cent Sci. 2022 Jan 26;8(1):57-66. doi: 10.1021/acscentsci.1c00434. Epub 2021 , Dec 22. PMID:35106373<ref>PMID:35106373</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7axs" style="background-color:#fffaf0;"></div>

==See Also==
*[[WD-repeat protein 3D structures|WD-repeat protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Essen L-O]]
[[Category: Werel L]]