7vln

NSD2-PWWP1 domain bound with an imidazol-5-yl benzonitrile compound

spinqualitylabelsall models 7vln, resolution 3.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7vln is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.09Å Ligands: 7QC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease 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 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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