View source for 6ogn


==Crystal structure of mouse protein arginine methyltransferase 7 in complex with SGC8158 chemical probe==
<StructureSection load='6ogn' size='340' side='right'caption='[[6ogn]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ogn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=6npg 6npg]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OGN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OGN 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]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MJ7:5-S-(4-{[(4-chloro[1,1-biphenyl]-3-yl)methyl]amino}butyl)-5-thioadenosine'>MJ7</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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=6ogn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ogn OCA], [https://pdbe.org/6ogn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ogn RCSB], [https://www.ebi.ac.uk/pdbsum/6ogn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ogn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ANM7_MOUSE ANM7_MOUSE] 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. Specifically mediates the symmetric dimethylation of histone H4 'Arg-3' to form H4R3me2s. Plays a role in gene imprinting by being recruited by CTCFL at the H19 imprinted control region (ICR) and methylating histone H4 to form H4R3me2s, possibly leading to recruit DNA methyltransferases at these sites. May also play a role in embryonic stem cell (ESC) pluripotency. Also able to mediate the arginine methylation of histone H2A and myelin basic protein (MBP) in vitro; the relevance of such results is however unclear in vivo (By similarity).<ref>PMID:17048991</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective, and cell-active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, which in cells is converted to SGC8158, a potent, SAM-competitive PRMT7 inhibitor. Inhibition or knockout of cellular PRMT7 results in drastically reduced levels of arginine monomethylated HSP70 family stress-associated proteins. Structural and biochemical analyses reveal that PRMT7-driven in vitro methylation of HSP70 at R469 requires an ATP-bound, open conformation of HSP70. In cells, SGC3027 inhibits methylation of both constitutive and inducible forms of HSP70, and leads to decreased tolerance for perturbations of proteostasis including heat shock and proteasome inhibitors. These results demonstrate a role for PRMT7 and arginine methylation in stress response.

Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response.,Szewczyk MM, Ishikawa Y, Organ S, Sakai N, Li F, Halabelian L, Ackloo S, Couzens AL, Eram M, Dilworth D, Fukushi H, Harding R, Dela Sena CC, Sugo T, Hayashi K, McLeod D, Zepeda C, Aman A, Sanchez-Osuna M, Bonneil E, Takagi S, Al-Awar R, Tyers M, Richard S, Takizawa M, Gingras AC, Arrowsmith CH, Vedadi M, Brown PJ, Nara H, Barsyte-Lovejoy D Nat Commun. 2020 May 14;11(1):2396. doi: 10.1038/s41467-020-16271-z. PMID:32409666<ref>PMID:32409666</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ogn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Arrowsmith CH]]
[[Category: Bountra C]]
[[Category: Dong A]]
[[Category: Edwards AM]]
[[Category: Halabelian L]]
[[Category: Hutchinson A]]
[[Category: Li Y]]
[[Category: Seitova A]]
[[Category: Zeng H]]