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| - | [[Image:2axb.gif|left|200px]] | |
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| - | {{Structure
| + | ==Crystal Structure Analysis Of A 2-O-[2-(methoxy)ethyl]-2-thiothymidine Modified Oligodeoxynucleotide Duplex== |
| - | |PDB= 2axb |SIZE=350|CAPTION= <scene name='initialview01'>2axb</scene>, resolution 1.61Å
| + | <StructureSection load='2axb' size='340' side='right'caption='[[2axb]], [[Resolution|resolution]] 1.61Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=DA:2'-DEOXYADENOSINE-5'-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2'-DEOXYCYTIDINE-5'-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2'-DEOXYGUANOSINE-5'-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5'-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=S2M:2'-O-[2-(METHOXY)ETHYL]-2-THIOTHYMIDINE-5'-MONOPHOSPHATE'>S2M</scene>
| + | <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> |
| - | |ACTIVITY=
| + | </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> |
| - | |GENE=
| + | <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> |
| - | |DOMAIN=
| + | <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> |
| - | |RELATEDENTRY=
| + | </table> |
| - | |RESOURCES=<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.ebi.ac.uk/pdbsum/2axb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2axb RCSB]</span>
| + | __TOC__ |
| - | }}
| + | </StructureSection> |
| - | | + | [[Category: Large Structures]] |
| - | '''Crystal Structure Analysis Of A 2-O-[2-(methoxy)ethyl]-2-thiothymidine Modified Oligodeoxynucleotide Duplex'''
| + | [[Category: Diop-Frimpong B]] |
| - | | + | [[Category: Egli M]] |
| - | | + | [[Category: Manoharan M]] |
| - | ==Overview==
| + | [[Category: Prakash TP]] |
| - | 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.
| + | [[Category: Rajeev KG]] |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | 2AXB is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AXB OCA].
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| - | | + | |
| - | ==Reference==
| + | |
| - | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16170156 16170156]
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| - | [[Category: Protein complex]] | + | |
| - | [[Category: Diop-Frimpong, B.]] | + | |
| - | [[Category: Egli, M.]] | + | |
| - | [[Category: Manoharan, M.]] | + | |
| - | [[Category: Prakash, T P.]] | + | |
| - | [[Category: Rajeev, K G.]] | + | |
| - | [[Category: dna]]
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| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:58:36 2008''
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