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| | ==Crystal Structure Analysis Of A 2-O-[2-(methoxy)ethyl]-2-thiothymidine Modified Oligodeoxynucleotide Duplex== | | ==Crystal Structure Analysis Of A 2-O-[2-(methoxy)ethyl]-2-thiothymidine Modified Oligodeoxynucleotide Duplex== |
| - | <StructureSection load='2axb' size='340' side='right' caption='[[2axb]], [[Resolution|resolution]] 1.61Å' scene=''> | + | <StructureSection load='2axb' size='340' side='right'caption='[[2axb]], [[Resolution|resolution]] 1.61Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2axb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AXB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AXB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2axb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AXB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AXB FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=S2M:2-O-[2-(METHOXY)ETHYL]-2-THIOTHYMIDINE-5-MONOPHOSPHATE'>S2M</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.61Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2axb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2axb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2axb RCSB], [http://www.ebi.ac.uk/pdbsum/2axb PDBsum]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=S2M:2-O-[2-(METHOXY)ETHYL]-2-THIOTHYMIDINE-5-MONOPHOSPHATE'>S2M</scene></td></tr> |
| - | <table>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2axb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2axb OCA], [https://pdbe.org/2axb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2axb RCSB], [https://www.ebi.ac.uk/pdbsum/2axb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2axb ProSAT]</span></td></tr> |
| - | <div style="background-color:#fffaf0;">
| + | </table> |
| - | == Publication Abstract from PubMed ==
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| - | Substitution of oxygen atoms by sulfur at various locations in the nucleic acid framework has led to analogs such as the DNA phosphorothioates and 4'-thio RNA. The phosphorothioates are excellent mimics of DNA, exhibit increased resistance to nuclease degradation compared with the natural counterpart, and have been widely used as first-generation antisense nucleic acid analogs for applications in vitro and in vivo. The 4'-thio RNA analog exhibits significantly enhanced RNA affinity compared with RNA, and shows potential for incorporation into siRNAs. 2-Thiouridine (s2U) and 5-methyl-2-thiouridine (m5s2U) are natural nucleotide analogs. s2U in tRNA confers greater specificity of codon-anticodon interactions by discriminating more strongly between A and G compared with U. 2-Thio modification preorganizes the ribose and 2'-deoxyribose sugars for a C3'-endo conformation, and stabilizes heteroduplexes composed of modified DNA and complementary RNA. Combination of the 2-thio and sugar 2'-O-modifications has been demonstrated to boost both thermodynamic stability and nuclease resistance. Using the 2'-O-[2-(methoxy)ethyl]-2-thiothymidine (m5s2Umoe) analog, we have investigated the consequences of the replacement of the 2-oxygen by sulfur for base-pair geometry and duplex conformation. The crystal structure of the A-form DNA duplex with sequence GCGTAT*ACGC (T* = m5s2Umoe) was determined at high resolution and compared with the structure of the corresponding duplex with T* = m5Umoe. Notable changes as a result of the incorporation of sulfur concern the base-pair parameter 'opening', an improvement of stacking in the vicinity of modified nucleotides as measured by base overlap, and a van der Waals interaction between sulfur atoms from adjacent m5s2Umoe residues in the minor groove. The structural data indicate only minor adjustments in the water structure as a result of the presence of sulfur. The observed small structural perturbations combined with the favorable consequences for pairing stability and nuclease resistance (when combined with 2'-O-modification) render 2-thiouracil-modified RNA a promising candidate for applications in RNAi.
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| - | Stabilizing contributions of sulfur-modified nucleotides: crystal structure of a DNA duplex with 2'-O-[2-(methoxy)ethyl]-2-thiothymidines.,Diop-Frimpong B, Prakash TP, Rajeev KG, Manoharan M, Egli M Nucleic Acids Res. 2005 Sep 16;33(16):5297-307. Print 2005. PMID:16170156<ref>PMID:16170156</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div> | + | |
| - | == References ==
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| - | <references/> | + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Diop-Frimpong, B.]] | + | [[Category: Large Structures]] |
| - | [[Category: Egli, M.]] | + | [[Category: Diop-Frimpong B]] |
| - | [[Category: Manoharan, M.]] | + | [[Category: Egli M]] |
| - | [[Category: Prakash, T P.]] | + | [[Category: Manoharan M]] |
| - | [[Category: Rajeev, K G.]] | + | [[Category: Prakash TP]] |
| - | [[Category: Dna]]
| + | [[Category: Rajeev KG]] |
