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| | ==Stereochemistry Modulates Stability of Reduced Inter-Strand Cross-Links Arising From R- and S-alpha-methyl-gamma-OH-1,N2-propano-2'-Deoxyguanine in the 5'-CpG-3' DNA Sequence== | | ==Stereochemistry Modulates Stability of Reduced Inter-Strand Cross-Links Arising From R- and S-alpha-methyl-gamma-OH-1,N2-propano-2'-Deoxyguanine in the 5'-CpG-3' DNA Sequence== |
| - | <StructureSection load='2hmd' size='340' side='right' caption='[[2hmd]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='2hmd' size='340' side='right'caption='[[2hmd]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2hmd]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HMD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2hmd]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HMD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HMD FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2EG:2-DEOXY-N-ETHYLGUANOSINE+5-PHOSPHATE'>2EG</scene></td></tr> | + | </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2hli|2hli]], [[2hmr|2hmr]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2EG:2-DEOXY-N-ETHYLGUANOSINE+5-PHOSPHATE'>2EG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hmd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2hmd RCSB], [http://www.ebi.ac.uk/pdbsum/2hmd PDBsum]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hmd OCA], [https://pdbe.org/2hmd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hmd RCSB], [https://www.ebi.ac.uk/pdbsum/2hmd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hmd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2hmd" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cho, Y J.]] | + | [[Category: Large Structures]] |
| - | [[Category: Harris, T M.]] | + | [[Category: Cho Y-J]] |
| - | [[Category: Kozekov, I D.]] | + | [[Category: Harris TM]] |
| - | [[Category: Rizzo, C J.]] | + | [[Category: Kozekov ID]] |
| - | [[Category: Stone, M P.]] | + | [[Category: Rizzo CJ]] |
| - | [[Category: Crotonaldehyde interstrand dna cross-link]]
| + | [[Category: Stone MP]] |
| - | [[Category: Dna]]
| + | |
| Structural highlights
Publication Abstract from PubMed
The solution structures of 5'-Cp-N2-dG-3'-R-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' and 5'-Cp-N2-dG-3'-S-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' interstrand DNA cross-links in the 5'-CpG-3' sequence were determined by NMR spectroscopy. These were utilized as chemically stable surrogates for the corresponding carbinolamine interstrand cross-links arising from the crotonaldehyde- and acetaldehyde-derived R- and S-alpha-CH3-gamma-OH-1,N2-propanodeoxyguanosine adducts. The results provide an explanation for the observation that interstrand cross-link formation in the 5'-CpG-3' sequence by the R- and S-alpha-CH3-gamma-OH-1,N2-propanodeoxyguanosine adducts is dependent upon stereochemistry, favoring the R-alpha-CH3-gamma-OH-1,N2-propanodeoxyguanosine adduct [Kozekov, I. D., Nechev, L. V., Moseley, M. S., Harris, C. M., Rizzo, C. J., Stone, M. P., and Harris, T. M. (2003) J. Am. Chem. Soc. 125, 50-61]. Molecular dynamics calculations, restrained by NOE-based distances and empirical restraints, revealed that both the 5'-Cp-N2-dG-3'-R-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' and 5'-Cp-N2-dG-3'-S-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' cross-links were located in the minor groove and retained Watson-Crick hydrogen bonds at the tandem cross-linked C.G base pairs. However, for the 5'-Cp-N2-dG-3'-R-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' cross-link, the (alpha)-CH3 group was positioned in the center of the minor groove, whereas for the 5'-Cp-N2-dG-3'-S-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' cross-link, the (alpha)-CH3 group was positioned in the 3' direction, showing steric interference with the DNA helix. The 5'-Cp-N2-dG-3'-S-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' cross-link exhibited a lower thermal stability as evidenced by NMR spectroscopy as a function of temperature. The two cross-links also exhibited apparent differences in the conformation of the interstrand three-carbon cross-link, which may also contribute to the lower apparent thermodynamic stability of the 5'-Cp-N2-dG-3'-S-(alpha)-CH3-propyl-5'-Cp-N2-dG-3' cross-link.
Stereochemistry modulates the stability of reduced interstrand cross-links arising from R- and S-alpha-CH3-gamma-OH-1,N2-propano-2'-deoxyguanosine in the 5'-CpG-3' DNA sequence.,Cho YJ, Kozekov ID, Harris TM, Rizzo CJ, Stone MP Biochemistry. 2007 Mar 13;46(10):2608-21. Epub 2007 Feb 17. PMID:17305317[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cho YJ, Kozekov ID, Harris TM, Rizzo CJ, Stone MP. Stereochemistry modulates the stability of reduced interstrand cross-links arising from R- and S-alpha-CH3-gamma-OH-1,N2-propano-2'-deoxyguanosine in the 5'-CpG-3' DNA sequence. Biochemistry. 2007 Mar 13;46(10):2608-21. Epub 2007 Feb 17. PMID:17305317 doi:http://dx.doi.org/10.1021/bi061381h
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