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| [[Image:1pyj.gif|left|200px]]<br /><applet load="1pyj" size="350" color="white" frame="true" align="right" spinBox="true"
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| caption="1pyj" />
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| '''Solution Structure of an O6-[4-oxo-4-(3-pyridyl)butyl]guanine adduct in an 11mer DNA duplex'''<br />
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| ==Overview== | | ==Solution Structure of an O6-[4-oxo-4-(3-pyridyl)butyl]guanine adduct in an 11mer DNA duplex== |
| The pyridyloxobutylating agents derived from metabolically activated tobacco-specific nitrosamines can covalently modify guanine bases in DNA at the O(6) position. The adduct formed, O(6)-[4-oxo-4-(3-pyridyl)butyl]guanine ([POB]dG), results in mutations that can lead to tumor formation, posing a significant cancer risk to humans exposed to tobacco smoke. A combined NMR-molecular mechanics computational approach was used to determine the solution structure of the [POB]dG adduct within an 11mer duplex sequence d(CCATAT-[POB]G-GCCC).d(GGGCCATATGG). In agreement with the NMR results, the POB ligand is located in the major groove, centered between the flanking 5'-side dT.dA and the 3'-side dG.dC base pairs and thus in the plane of the modified [POB]dG.dC base pair, which is displaced slightly into the minor groove. The modified base pair in the structure adopts wobble base pairing (hydrogen bonds between [POB]dG(N1) and dC(NH4) amino proton and between [POB]dG(NH2) amino proton and dC(N3)). A hydrogen bond appears to occur between the POB carbonyl oxygen and the partner dC's second amino proton. The modified guanine purine base, partner cytosine pyrimidine base, and POB pyridyl ring form a triplex via this unusual hydrogen-bonding pattern. The phosphodiester backbone twists at the lesion site, accounting for the unusual phosphorus chemical shift differences relative to those for the control DNA duplex. The helical distortions and wobble base pairing induced by the covalent binding of POB to the O(6)-position of dG help explain the significant decrease of 17.6 degrees C in melting temperature of the modified duplex relative to the unmodified control.
| | <StructureSection load='1pyj' size='340' side='right'caption='[[1pyj]]' scene=''> |
| | | == Structural highlights == |
| ==About this Structure== | | <table><tr><td colspan='2'>[[1pyj]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PYJ FirstGlance]. <br> |
| 1PYJ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=PBO:'>PBO</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PYJ OCA].
| | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XPB:O6-[4-OXO-4-(3-PYRIDYL)BUTYL]-2-DEOXYGUANOSINE-5-MONOPHOSPHATE'>XPB</scene></td></tr> |
| ==Reference==
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1pyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pyj OCA], [https://pdbe.org/1pyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pyj RCSB], [https://www.ebi.ac.uk/pdbsum/1pyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pyj ProSAT]</span></td></tr> |
| Solution structure of an O6-[4-oxo-4-(3-pyridyl)butyl]guanine adduct in an 11 mer DNA duplex: evidence for formation of a base triplex., Peterson LA, Vu C, Hingerty BE, Broyde S, Cosman M, Biochemistry. 2003 Nov 18;42(45):13134-44. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14609323 14609323]
| | </table> |
| [[Category: Protein complex]] | | __TOC__ |
| [[Category: Broyde, S.]] | | </StructureSection> |
| [[Category: Cosman, M.]] | | [[Category: Large Structures]] |
| [[Category: Hingerty, B E.]] | | [[Category: Broyde S]] |
| [[Category: Peterson, L A.]] | | [[Category: Cosman M]] |
| [[Category: Vu, C.]] | | [[Category: Hingerty BE]] |
| [[Category: PBO]]
| | [[Category: Peterson LA]] |
| [[Category: dna adduct]]
| | [[Category: Vu C]] |
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| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:33:53 2008''
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