7u30
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==PRMT5:MEP50 Complexed with Cyclonucleoside Compound 1== | |
| + | <StructureSection load='7u30' size='340' side='right'caption='[[7u30]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7u30]] 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=7U30 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7U30 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]] 2.6Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=LB3:(9R,10R,11S,12R,13R,14R)-4-amino-9-(3,4-difluorophenyl)-6,7,8,9,10,11,12,13-octahydro-10,13-epoxy[1,3]diazecino[1,2-e]purine-11,12-diol'>LB3</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=7u30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7u30 OCA], [https://pdbe.org/7u30 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7u30 RCSB], [https://www.ebi.ac.uk/pdbsum/7u30 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7u30 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ANM5_HUMAN ANM5_HUMAN] Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA. Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles. Methylates SUPT5H. Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. Plays a role in the assembly of snRNP core particles. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. May regulate the SUPT5H transcriptional elongation properties. May be part of a pathway that is connected to a chloride current, possibly through cytoskeletal rearrangement. Methylates histone H2A and H4 'Arg-3' during germ cell development. Methylates histone H3 'Arg-8', which may repress transcription. Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage. Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation. Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity. Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9. Methylates and regulates SRGAP2 which is involved in cell migration and differentiation. Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter.<ref>PMID:10531356</ref> <ref>PMID:11152681</ref> <ref>PMID:11747828</ref> <ref>PMID:12411503</ref> <ref>PMID:15737618</ref> <ref>PMID:17709427</ref> <ref>PMID:20159986</ref> <ref>PMID:20810653</ref> <ref>PMID:21258366</ref> <ref>PMID:21917714</ref> <ref>PMID:22269951</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Synthesis of medium-sized rings is known to be challenging due to high transannular strain especially for 9- and 10-membered rings. Herein we report design and synthesis of unprecedented 9- and 10-membered purine 8,5'-cyclonucleosides as the first cyclonucleoside PRMT5 inhibitors. The cocrystal structure of PRMT5:MEP50 in complex with the synthesized 9-membered cyclonucleoside 1 revealed its binding mode in the SAM binding pocket of PRMT5. | ||
| - | + | Design and synthesis of unprecedented 9- and 10-membered cyclonucleosides with PRMT5 inhibitory activity.,Kawamura S, Palte RL, Kim HY, Sauri J, Sondey C, Mansueto MS, Altman MD, Machacek MR Bioorg Med Chem. 2022 Jul 15;66:116820. doi: 10.1016/j.bmc.2022.116820. Epub 2022 , May 14. PMID:35594650<ref>PMID:35594650</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7u30" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Palte RL]] | ||
Current revision
PRMT5:MEP50 Complexed with Cyclonucleoside Compound 1
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