View source for 4ryl


==Human Protein Arginine Methyltransferase 3 in complex with 1-isoquinolin-6-yl-3-[2-oxo-2-(pyrrolidin-1-yl)ethyl]urea==
<StructureSection load='4ryl' size='340' side='right'caption='[[4ryl]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ryl]] is a 1 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=4RYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RYL 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3ZG:1-ISOQUINOLIN-6-YL-3-[2-OXO-2-(PYRROLIDIN-1-YL)ETHYL]UREA'>3ZG</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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=4ryl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ryl OCA], [https://pdbe.org/4ryl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ryl RCSB], [https://www.ebi.ac.uk/pdbsum/4ryl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ryl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ANM3_HUMAN ANM3_HUMAN] Methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in some proteins.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
PRMT3 catalyzes the asymmetric dimethylation of arginine residues of various proteins. It is essential for maturation of ribosomes, may have a role in lipogenesis, and is implicated in several diseases. A potent, selective, and cell-active PRMT3 inhibitor would be a valuable tool for further investigating PRMT3 biology. Here we report the discovery of the first PRMT3 chemical probe, SGC707, by structure-based optimization of the allosteric PRMT3 inhibitors we reported previously, and thorough characterization of this probe in biochemical, biophysical, and cellular assays. SGC707 is a potent PRMT3 inhibitor (IC50 =31+/-2 nM, KD =53+/-2 nM) with outstanding selectivity (selective against 31 other methyltransferases and more than 250 non-epigenetic targets). The mechanism of action studies and crystal structure of the PRMT3-SGC707 complex confirm the allosteric inhibition mode. Importantly, SGC707 engages PRMT3 and potently inhibits its methyltransferase activity in cells. It is also bioavailable and suitable for animal studies. This well-characterized chemical probe is an excellent tool to further study the role of PRMT3 in health and disease.

A Potent, Selective and Cell-Active Allosteric Inhibitor of Protein Arginine Methyltransferase 3 (PRMT3).,Kaniskan HU, Szewczyk MM, Yu Z, Eram MS, Yang X, Schmidt K, Luo X, Dai M, He F, Zang I, Lin Y, Kennedy S, Li F, Dobrovetsky E, Dong A, Smil D, Min SJ, Landon M, Lin-Jones J, Huang XP, Roth BL, Schapira M, Atadja P, Barsyte-Lovejoy D, Arrowsmith CH, Brown PJ, Zhao K, Jin J, Vedadi M Angew Chem Int Ed Engl. 2015 Feb 27. doi: 10.1002/anie.201412154. PMID:25728001<ref>PMID:25728001</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ryl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arrowsmith CH]]
[[Category: Atadja P]]
[[Category: Barsyte-Lovejoy D]]
[[Category: Bountra C]]
[[Category: Brown PJ]]
[[Category: Dai M]]
[[Category: Dobrovetsky E]]
[[Category: Dong A]]
[[Category: Edwards AM]]
[[Category: Eram MS]]
[[Category: He F]]
[[Category: Huang XP]]
[[Category: Jin J]]
[[Category: Kaniskan HU]]
[[Category: Kennedy S]]
[[Category: Landon M]]
[[Category: Li F]]
[[Category: Lin Y]]
[[Category: Lin-Jones J]]
[[Category: Luo X]]
[[Category: Min SJ]]
[[Category: Roth BL]]
[[Category: Schapira M]]
[[Category: Schmidt K]]
[[Category: Smil D]]
[[Category: Szewczyk M]]
[[Category: Tempel W]]
[[Category: Vedadi M]]
[[Category: Yang X]]
[[Category: Yu Z]]
[[Category: Zang I]]
[[Category: Zhao K]]