7vln
From Proteopedia
(Difference between revisions)
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==NSD2-PWWP1 domain bound with an imidazol-5-yl benzonitrile compound== | ==NSD2-PWWP1 domain bound with an imidazol-5-yl benzonitrile compound== | ||
| - | <StructureSection load='7vln' size='340' side='right'caption='[[7vln]]' scene=''> | + | <StructureSection load='7vln' size='340' side='right'caption='[[7vln]], [[Resolution|resolution]] 3.09Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VLN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VLN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7vln]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VLN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VLN FirstGlance]. <br> |
| - | </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=7vln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vln OCA], [https://pdbe.org/7vln PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vln RCSB], [https://www.ebi.ac.uk/pdbsum/7vln PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vln ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7QC:4-[5-[4-(aminomethyl)-2,6-dimethoxy-phenyl]-3-methyl-imidazol-4-yl]benzenecarbonitrile'>7QC</scene></td></tr> |
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/[Histone_H3]-lysine(36)_N-dimethyltransferase [Histone H3]-lysine(36) N-dimethyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.357 2.1.1.357] </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=7vln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vln OCA], [https://pdbe.org/7vln PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vln RCSB], [https://www.ebi.ac.uk/pdbsum/7vln PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vln ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [[https://www.uniprot.org/uniprot/NSD2_HUMAN NSD2_HUMAN]] Wolf-Hirschhorn syndrome. A chromosomal aberration involving WHSC1 is a cause of multiple myeloma tumors. Translocation t(4;14)(p16.3;q32.3) with IgH. WHSC1 is located in the Wolf-Hirschhorn syndrome (WHS) critical region. WHS results from by sub-telomeric deletions in the short arm of chromosome 4. WHSC1 is deleted in every case, however deletion of linked genes contributes to both the severity of the core characteristics and the presence of the additional syndromic problems. | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/NSD2_HUMAN NSD2_HUMAN]] Histone methyltransferase with histone H3 'Lys-27' (H3K27me) methyltransferase activity. Isoform 2 may act as a transcription regulator that binds DNA and suppresses IL5 transcription through HDAC recruitment.<ref>PMID:11152655</ref> <ref>PMID:16115125</ref> <ref>PMID:18172012</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Overexpression, point mutations, or translocations of protein lysine methyltransferase NSD2 occur in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of multiple domains including a SET catalytic domain and two PWWP domains binding to methylated histone proteins. Here, we reported our efforts to develop a series of NSD2-PWWP1 inhibitors, and further structure-based optimization resulted in a potent inhibitor 38, which has high selectivity toward the NSD2-PWWP1 domain. The detailed biological evaluation revealed that compound 38 can bind to NSD2-PWWP1 and then affect the expression of genes regulated by NSD2. The current discovery will provide a useful chemical probe to the future research in understanding the specific regulation mode of NSD2 by PWWP1 recognition and pave the way to develop potential drugs targeting NSD2 protein. | ||
| + | |||
| + | Structure-Based Discovery of a Series of NSD2-PWWP1 Inhibitors.,Li N, Yang H, Liu K, Zhou L, Huang Y, Cao D, Li Y, Sun Y, Yu A, Du Z, Yu F, Zhang Y, Wang B, Geng M, Li J, Xiong B, Xu S, Huang X, Liu T J Med Chem. 2022 Jun 15. doi: 10.1021/acs.jmedchem.2c00709. PMID:35704853<ref>PMID:35704853</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7vln" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Cao | + | [[Category: Cao, D Y]] |
| - | [[Category: Li J]] | + | [[Category: Li, J]] |
| - | [[Category: Li | + | [[Category: Li, Y L]] |
| - | [[Category: Xiong B]] | + | [[Category: Xiong, B]] |
| + | [[Category: Histone-lysine n-methyltransferase nsd2]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 05:28, 13 July 2022
NSD2-PWWP1 domain bound with an imidazol-5-yl benzonitrile compound
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