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==Crystal Structure of WHSC1L1 in Complex with Inhibitor PEP21== | ==Crystal Structure of WHSC1L1 in Complex with Inhibitor PEP21== | ||
<StructureSection load='6cen' size='340' side='right' caption='[[6cen]], [[Resolution|resolution]] 1.61Å' scene=''> | <StructureSection load='6cen' size='340' side='right'caption='[[6cen]], [[Resolution|resolution]] 1.61Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6cen]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6cen]] 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=6CEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CEN FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.61Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <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'>[https://proteopedia.org/fgij/fg.htm?mol=6cen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cen OCA], [https://pdbe.org/6cen PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cen RCSB], [https://www.ebi.ac.uk/pdbsum/6cen PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cen ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/NSD3_HUMAN NSD3_HUMAN] Note=Defects in WHSC1L1 may be involved in non small cell lung carcinomas (NSCLC). Amplified or overexpressed in NSCLC.<ref>PMID:15983384</ref> Note=A chromosomal aberration involving WHSC1L1 is found in childhood acute myeloid leukemia. Translocation t(8;11)(p11.2;p15) with NUP98. | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/NSD3_HUMAN NSD3_HUMAN] Histone methyltransferase. Preferentially methylates 'Lys-4' and 'Lys-27' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression.<ref>PMID:16682010</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 21: | ||
</div> | </div> | ||
<div class="pdbe-citations 6cen" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6cen" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Boriack-Sjodin | [[Category: Boriack-Sjodin PA]] | ||
[[Category: Farrow | [[Category: Farrow NA]] | ||
[[Category: Swinger | [[Category: Swinger K]] | ||
Latest revision as of 10:51, 17 October 2024
Crystal Structure of WHSC1L1 in Complex with Inhibitor PEP21Crystal Structure of WHSC1L1 in Complex with Inhibitor PEP21
Structural highlights
DiseaseNSD3_HUMAN Note=Defects in WHSC1L1 may be involved in non small cell lung carcinomas (NSCLC). Amplified or overexpressed in NSCLC.[1] Note=A chromosomal aberration involving WHSC1L1 is found in childhood acute myeloid leukemia. Translocation t(8;11)(p11.2;p15) with NUP98. FunctionNSD3_HUMAN Histone methyltransferase. Preferentially methylates 'Lys-4' and 'Lys-27' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression.[2] Publication Abstract from PubMedWHSC1 is a histone methyltransferase that is responsible for mono- and dimethylation of lysine 36 on histone H3 and has been implicated as a driver in a variety of hematological and solid tumors. Currently, there is a complete lack of validated chemical matter for this important drug discovery target. Herein we report on the first fully validated WHSC1 inhibitor, PTD2, a norleucine-containing peptide derived from the histone H4 sequence. This peptide exhibits micromolar affinity towards WHSC1 in biochemical and biophysical assays. Furthermore, a crystal structure was solved with the peptide in complex with SAM and the SET domain of WHSC1L1. This inhibitor is an important first step in creating potent, selective WHSC1 tool compounds for the purposes of understanding the complex biology in relation to human disease. Identification of a peptide inhibitor for the histone methyltransferase WHSC1.,Morrison MJ, Boriack-Sjodin PA, Swinger KK, Wigle TJ, Sadalge D, Kuntz KW, Scott MP, Janzen WP, Chesworth R, Duncan KW, Harvey DM, Lampe JW, Mitchell LH, Copeland RA PLoS One. 2018 May 9;13(5):e0197082. doi: 10.1371/journal.pone.0197082., eCollection 2018. PMID:29742153[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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