9q0i: Difference between revisions
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New page: '''Unreleased structure''' The entry 9q0i is ON HOLD Authors: Jauregui Matos, V., Fisher, A.J., Beal, P.A. Description: Structure of dsRNA 16mer containing 4''-C-methyladenosine [[Cate... |
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==Structure of dsRNA 16mer containing 4'-C-methyladenosine== | |||
<StructureSection load='9q0i' size='340' side='right'caption='[[9q0i]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9q0i]] is a 6 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=9Q0I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Q0I 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]] 1.801Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5BU:5-BROMO-URIDINE-5-MONOPHOSPHATE'>5BU</scene>, <scene name='pdbligand=A1CNL:9-{(4xi)-5-deoxy-4-[(phosphonooxy)methyl]-alpha-L-lyxofuranosyl}-9H-purin-6-amine'>A1CNL</scene>, <scene name='pdbligand=SPM:SPERMINE'>SPM</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=9q0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9q0i OCA], [https://pdbe.org/9q0i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9q0i RCSB], [https://www.ebi.ac.uk/pdbsum/9q0i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9q0i ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Oligonucleotides capable of guiding adenosine deaminases acting on RNA (ADARs) to carry out therapeutic adenosine (A) to inosine (I) editing constitute a promising new class of nucleic acid therapeutics. However, our understanding of the impact of different chemical modifications at the various nucleotide positions in ADAR guide strands is limited. While ribose 2' modification is common in ADAR-directing guides, less is known about the impact of modification at the 4' position. Here we describe the synthesis of several 4'-Calpha-methyl and 2'-O, 4'-Calpha-dimethyl derivatives of adenosine, uridine, and cytidine and their incorporation into RNA. In addition, we show that these analogs maintain the base pairing selectivity of their parent nucleoside and modulate duplex thermal stability in an analog-dependent manner. High-resolution crystal structures of RNA duplexes bearing 4'-Calpha-methyl A or U showed that these analogs adopt a C3'-endo sugar pucker and project 4' substituents into the minor groove. Finally, we find that 2'-O, 4'-Calpha-dimethyluridine and 2'-O, 4'-Calpha-dimethyladenosine strategically positioned in ADAR guide strands can increase the selectivity of the editing reaction for target sequences with adjacent off-target adenosines. This work advances our understanding of the ADAR reaction mechanism and informs the design of ADAR guide strands with improved selectivity. | |||
Synthesis of 2'-O,4'-Calpha-Dimethyl Ribonucleoside Analogs and Their Effects on RNA and Modulation of ADAR Editing.,Jauregui-Matos V, Brinkman HF, Salvador PJ, Jacobs O, Cheng J, Mozumder S, Vu T, Fisher AJ, Beal PA Chemistry. 2026 Jan 2;32(1):e02958. doi: 10.1002/chem.202502958. Epub 2025 Nov , 29. PMID:41318945<ref>PMID:41318945</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 9q0i" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Jauregui Matos | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Beal PA]] | |||
[[Category: Fisher AJ]] | |||
[[Category: Jauregui Matos V]] | |||
Latest revision as of 08:14, 29 April 2026
Structure of dsRNA 16mer containing 4'-C-methyladenosine
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