View source for 8qmh


==Crystal structure of RNA G2C4 repeats in complex with small synthetic molecule ANP77==
<StructureSection load='8qmh' size='340' side='right'caption='[[8qmh]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8qmh]] is a 4 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=8QMH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QMH 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]] 1.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=W53:3-(7-azanyl-1,8-naphthyridin-2-yl)-2-[(7-azanyl-1,8-naphthyridin-2-yl)methyl]-~{N}-(3-azanylpropyl)propanamide'>W53</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=8qmh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qmh OCA], [https://pdbe.org/8qmh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qmh RCSB], [https://www.ebi.ac.uk/pdbsum/8qmh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qmh ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The abnormal expansion of GGGGCC/GGCCCC hexanucleotide repeats (HR) in C9orf72 is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Structural polymorphisms of HR result in the multifactorial pathomechanism of ALS/FTD. Consequently, many ongoing studies are focused at developing therapies targeting pathogenic HR RNA. One of them involves small molecules blocking sequestration of important proteins, preventing formation of toxic nuclear foci. However, rational design of potential therapeutics is hindered by limited number of structural studies of RNA-ligand complexes. We determined the crystal structure of antisense HR RNA in complex with ANP77 ligand (1.1 A resolution) and in the free form (0.92 and 1.5 A resolution). HR RNA folds into a triplex structure composed of four RNA chains. ANP77 interacted with two neighboring single-stranded cytosines to form pseudo-canonical base pairs by adopting sandwich-like conformation and adjusting the position of its naphthyridine units to the helical twist of the RNA. In the unliganded structure, the cytosines formed a peculiar triplex i-motif, assembled by trans C*C+ pair and a third cytosine located at the Hoogsteen edge of the C*C+ pair. These results extend our knowledge of the structural polymorphisms of HR and can be used for rational design of small molecules targeting disease-related RNAs.

Antisense RNA C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms a triplex-like structure and binds small synthetic ligand.,Blaszczyk L, Ryczek M, Das B, Mateja-Pluta M, Bejger M, Sliwiak J, Nakatani K, Kiliszek A Nucleic Acids Res. 2024 Jun 24;52(11):6707-6717. doi: 10.1093/nar/gkae376. PMID:38738637<ref>PMID:38738637</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8qmh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Blaszczyk L]]
[[Category: Kiliszek A]]
[[Category: Ryczek M]]