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| [[Image:412d.gif|left|200px]]
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| {{Structure
| | ==DUPLEX [5'-D(GCGTA+TACGC)]2 WITH INCORPORATED 2'-O-METHYL-[TRI(OXYETHYL)] RIBONUCLEOSIDE== |
| |PDB= 412d |SIZE=350|CAPTION= <scene name='initialview01'>412d</scene>, resolution 1.650Å
| | <StructureSection load='412d' size='340' side='right'caption='[[412d]], [[Resolution|resolution]] 1.65Å' scene=''> |
| |SITE=
| | == Structural highlights == |
| |LIGAND= <scene name='pdbligand=126:2'-O-METHYL-[TRI(OXYETHYL)]-5-METHYL-URIDINE-5'-MONOPHOSPHATE'>126</scene>, <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=MG:MAGNESIUM+ION'>MG</scene>
| | <table><tr><td colspan='2'>[[412d]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=412D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=412D 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]] 1.65Å</td></tr> |
| |GENE=
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=126:2-O-METHYL-[TRI(OXYETHYL)]-5-METHYL-URIDINE-5-MONOPHOSPHATE'>126</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=412d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=412d OCA], [https://pdbe.org/412d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=412d RCSB], [https://www.ebi.ac.uk/pdbsum/412d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=412d ProSAT]</span></td></tr> |
| |RELATEDENTRY=
| | </table> |
| |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=412d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=412d OCA], [http://www.ebi.ac.uk/pdbsum/412d PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=412d RCSB]</span>
| | __TOC__ |
| }}
| | </StructureSection> |
| | | [[Category: Large Structures]] |
| '''DUPLEX [5'-D(GCGTA+TACGC)]2 WITH INCORPORATED 2'-O-METHYL-[TRI(OXYETHYL)] RIBONUCLEOSIDE'''
| | [[Category: Altmann KH]] |
| | | [[Category: Egli M]] |
| | | [[Category: Martin P]] |
| ==Overview==
| | [[Category: Natt F]] |
| Chemically modified nucleic acids are currently being evaluated as potential antisense compounds for therapeutic applications. 2'-O-Ethylene glycol substituted oligoribonucleotides are second-generation antisense inhibitors of gene expression with promising features for in vivo use. Relative to DNA, they display improved RNA affinity and higher nuclease resistance. Moreover, chimeric oligonucleotides with 2'-O-methoxyethyl ribonucleoside wings and a central DNA phosphorothioate window have been shown to effectively reduce the growth of tumors in animal models at low doses. Using X-ray crystallography, we have determined the structures of three A-form DNA duplexes containing the following 2'-O-modified ribothymidine building blocks: 2'-O-methoxyethyl ribo-T, 2'-O-methyl[tri(oxyethyl)] ribo-T, and 2'-O-ethoxymethylene ribo-T. In contrast to 2'-O-ethylene glycol substituents, the presence of a 2'-O-ethoxymethylene group leads to slightly reduced RNA affinity of the corresponding oligonucleotides. The three structures allow a qualitative rationalization of the differing stabilities of duplexes between oligonucleotides comprising these types of 2'-O-modified ribonucleotides and complementary RNAs. The stabilizing 2'-O-ethylene glycol substituents are conformationally preorganized for the duplex state. Thus, the presence of one or several ethylene glycol moieties may reduce the conformational space of the substituents in an oligonucleotide single strand. In addition, most of these preferred conformations appear to be compatible with the minor groove topology in an A-type duplex. Factors that contribute to the conformational rigidity of the 2'-O-substituents are anomeric and gauche effects, electrostatic interactions between backbone and substituent, and bound water molecules.
| | [[Category: Portmann S]] |
| | | [[Category: Tay EC]] |
| ==About this Structure==
| | [[Category: Tereshko V]] |
| 412D 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=412D OCA].
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| ==Reference==
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| Correlating structure and stability of DNA duplexes with incorporated 2'-O-modified RNA analogues., Tereshko V, Portmann S, Tay EC, Martin P, Natt F, Altmann KH, Egli M, Biochemistry. 1998 Jul 28;37(30):10626-34. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9692952 9692952]
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| [[Category: Protein complex]] | |
| [[Category: Altmann, K H.]] | |
| [[Category: Egli, M.]] | |
| [[Category: Martin, P.]] | |
| [[Category: Natt, F.]] | |
| [[Category: Portmann, S.]] | |
| [[Category: Tay, E C.]] | |
| [[Category: Tereshko, V.]] | |
| [[Category: duplex [5'-d(gcgta+tacgc)]2 with incorporated 2'-o-methyl-[tri(oxyethyl)] ribonucleoside]]
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| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:36:55 2008''
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