View source for 4qq6


==Crystal Structure of tudor domain of SMN1 in complex with a small organic molecule==
<StructureSection load='4qq6' size='340' side='right'caption='[[4qq6]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4qq6]] 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=4QQ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QQ6 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]] 1.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=36X:4-METHYL-2,3,4,5,6,7-HEXAHYDRODICYCLOPENTA[B,E]PYRIDIN-8(1H)-IMINE'>36X</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=4qq6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qq6 OCA], [https://pdbe.org/4qq6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qq6 RCSB], [https://www.ebi.ac.uk/pdbsum/4qq6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qq6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SMN_HUMAN SMN_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Survival of motor neuron (SMN) functions in diverse biological pathways via recognition of symmetric dimethylarginine (Rme2s) on proteins by its Tudor domain, and deficiency of SMN leads to spinal muscular atrophy. Here we report a potent and selective antagonist with a 4-iminopyridine scaffold targeting the Tudor domain of SMN. Our structural and mutagenesis studies indicate that both the aromatic ring and imino groups of compound 1 contribute to its selective binding to SMN. Various on-target engagement assays support that compound 1 specifically recognizes SMN in a cellular context and prevents the interaction of SMN with the R1810me2s of RNA polymerase II subunit POLR2A, resulting in transcription termination and R-loop accumulation mimicking SMN depletion. Thus, in addition to the antisense, RNAi and CRISPR/Cas9 techniques, potent SMN antagonists could be used as an efficient tool to understand the biological functions of SMN.

A small molecule antagonist of SMN disrupts the interaction between SMN and RNAP II.,Liu Y, Iqbal A, Li W, Ni Z, Wang Y, Ramprasad J, Abraham KJ, Zhang M, Zhao DY, Qin S, Loppnau P, Jiang H, Guo X, Brown PJ, Zhen X, Xu G, Mekhail K, Ji X, Bedford MT, Greenblatt JF, Min J Nat Commun. 2022 Sep 16;13(1):5453. doi: 10.1038/s41467-022-33229-5. PMID:36114190<ref>PMID:36114190</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4qq6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arrowsmith CH]]
[[Category: Bountra C]]
[[Category: Brown PJ]]
[[Category: Edwards AM]]
[[Category: Iqbal A]]
[[Category: Liu Y]]
[[Category: Min J]]
[[Category: Tempel W]]
[[Category: Walker JR]]