1ei4

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(New page: 200px<br /><applet load="1ei4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ei4, resolution 1.43&Aring;" /> '''B-DNA DODECAMER CGCG...)
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[[Image:1ei4.gif|left|200px]]<br /><applet load="1ei4" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ei4, resolution 1.43&Aring;" />
 
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'''B-DNA DODECAMER CGCGAAT(TLC)CGCG WITH INCORPORATED [3.3.0]BICYCLO-ARABINO-THYMINE-5'-PHOSPHATE'''<br />
 
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==Overview==
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==B-DNA DODECAMER CGCGAAT(TLC)CGCG WITH INCORPORATED [3.3.0]BICYCLO-ARABINO-THYMINE-5'-PHOSPHATE==
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The origins of the substrate specificity of Escherichia coli RNase H1, (termed RNase H here), an enzyme that hydrolyzes the RNA strand of DNA-RNA, hybrids, are not understood at present. Although the enzyme binds, double-stranded RNA, no cleavage occurs with such duplexes [Lima, W. F., and Crooke, S. T. (1997) Biochemistry 36, 390]. Therefore, the hybrid, substrates may not adopt a canonical A-form geometry. Furthermore, RNase H, is exquisitely sensitive to chemical modification of the DNA strands in, hybrid duplexes. This is particularly relevant to the RNase H-dependent, pathway of antisense action. Thus, only very few of the modifications, currently being evaluated as antisense therapeutics are tolerated by the, enzyme, among them phosphorothioate DNA (PS-DNA). Recently, hybrids of RNA, and arabinonucleic acid (ANA) as well as the 2'F-ANA analogue were shown, to be substrates of RNase H [Damha, M. J., et al. (1998) J. Am. Chem. Soc., 120, 12976]. Using X-ray crystallography, we demonstrate here that ANA, analogues, such as 2'F-ANA [Berger, I., et al. (1998) Nucleic Acids Res., 26, 2473] and [3.3.0]bicyclo-ANA (bc-ANA), may not be able to adopt sugar, puckers that are compatible with pure A- or a B-form duplex geometries, but rather prefer the intermediate O4'-endo conformation. On the basis of, the observed conformations of these ANA analogues in a DNA dodecamer, duplex, we have modeled a duplex of an all-C3'-endo RNA strand and an, all-O4'-endo 2'F-ANA strand. This duplex exhibits a minor groove width, that is intermediate between that of A-form RNA and B-form DNA, a feature, that may be exploited by the enzyme in differentiating between RNA, duplexes and DNA-RNA hybrids. Therefore, the combination of the, established structural and functional properties of ANA analogues helps, settle existing controversies concerning the discrimination of substrates, by RNase H. Knowlegde of the structure of an analogue that exhibits, enhanced RNA affinity while not interfering with RNase H activity may, prove helpful in the design of future antisense modifications.
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<StructureSection load='1ei4' size='340' side='right'caption='[[1ei4]], [[Resolution|resolution]] 1.43&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[1ei4]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EI4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EI4 FirstGlance]. <br>
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1EI4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with SPM and MG as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EI4 OCA].
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.43&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SPM:SPERMINE'>SPM</scene>, <scene name='pdbligand=TLC:2-O,3-ETHDIYL-ARABINOFURANOSYL-THYMINE-5-MONOPHOSPHATE'>TLC</scene></td></tr>
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==Reference==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ei4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ei4 OCA], [https://pdbe.org/1ei4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ei4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ei4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ei4 ProSAT]</span></td></tr>
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Structural basis of cleavage by RNase H of hybrids of arabinonucleic acids and RNA., Minasov G, Teplova M, Nielsen P, Wengel J, Egli M, Biochemistry. 2000 Apr 4;39(13):3525-32. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10736151 10736151]
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</table>
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[[Category: Protein complex]]
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__TOC__
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[[Category: Egli, M.]]
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</StructureSection>
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[[Category: Minasov, G.]]
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[[Category: Large Structures]]
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[[Category: Nielsen, P.]]
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[[Category: Egli M]]
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[[Category: Teplova, M.]]
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[[Category: Minasov G]]
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[[Category: Wengel, J.]]
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[[Category: Nielsen P]]
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[[Category: MG]]
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[[Category: Teplova M]]
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[[Category: SPM]]
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[[Category: Wengel J]]
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[[Category: [3.3.0]bicyclo-arabinonucleic acid]]
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[[Category: modified b-dodecamer]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 22:19:30 2007''
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Current revision

B-DNA DODECAMER CGCGAAT(TLC)CGCG WITH INCORPORATED [3.3.0]BICYCLO-ARABINO-THYMINE-5'-PHOSPHATE

PDB ID 1ei4

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