View source for 6wy3


==Crystal structure of RNA-10mer: CCGG(N4,N4-dimethyl-C)GCCGG; P212121 form==
<StructureSection load='6wy3' size='340' side='right'caption='[[6wy3]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wy3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WY3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WY3 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]] 1.647&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LV2:[(2~{R},3~{S},4~{R},5~{R})-5-[4-(dimethylamino)-2-oxidanylidene-pyrimidin-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>LV2</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=6wy3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wy3 OCA], [https://pdbe.org/6wy3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wy3 RCSB], [https://www.ebi.ac.uk/pdbsum/6wy3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wy3 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The N4-methylation of cytidine (m4C and m42C) in RNA plays important roles in both bacterial and eukaryotic cells. In this work, we synthesized a series of m4C and m42C modified RNA oligonucleotides, conducted their base pairing and bioactivity studies, and solved three new crystal structures of the RNA duplexes containing these two modifications. Our thermostability and X-ray crystallography studies, together with the molecular dynamic simulation studies, demonstrated that m4C retains a regular C:G base pairing pattern in RNA duplex and has a relatively small effect on its base pairing stability and specificity. By contrast, the m42C modification disrupts the C:G pair and significantly decreases the duplex stability through a conformational shift of native Watson-Crick pair to a wobble-like pattern with the formation of two hydrogen bonds. This double-methylated m42C also results in the loss of base pairing discrimination between C:G and other mismatched pairs like C:A, C:T and C:C. The biochemical investigation of these two modified residues in the reverse transcription model shows that both mono- or di-methylated cytosine bases could specify the C:T pair and induce the G to T mutation using HIV-1 RT. In the presence of other reverse transcriptases with higher fidelity like AMV-RT, the methylation could either retain the normal nucleotide incorporation or completely inhibit the DNA synthesis. These results indicate the methylation at N4-position of cytidine is a molecular mechanism to fine tune base pairing specificity and affect the coding efficiency and fidelity during gene replication.

Base pairing, structural and functional insights into N4-methylcytidine (m4C) and N4,N4-dimethylcytidine (m42C) modified RNA.,Mao S, Sekula B, Ruszkowski M, Ranganathan SV, Haruehanroengra P, Wu Y, Shen F, Sheng J Nucleic Acids Res. 2020 Oct 9;48(18):10087-10100. doi: 10.1093/nar/gkaa737. PMID:32941619<ref>PMID:32941619</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wy3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Haruehanroengra P]]
[[Category: Mao S]]
[[Category: Ruszkowski M]]
[[Category: Sekula B]]
[[Category: Sheng J]]