1hz2
From Proteopedia
(New page: 200px<br /><applet load="1hz2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hz2" /> '''SOLUTION NMR STRUCTURE OF SELF-COMPLEMENTARY...) |
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'''SOLUTION NMR STRUCTURE OF SELF-COMPLEMENTARY DUPLEX 5'-D(AGGCG*CCT)2 CONTAINING A TRIMETHYLENE CROSSLINK AT THE N2 POSITION OF G*. MODEL OF A MALONDIALDEHYDE CROSSLINK'''<br /> | '''SOLUTION NMR STRUCTURE OF SELF-COMPLEMENTARY DUPLEX 5'-D(AGGCG*CCT)2 CONTAINING A TRIMETHYLENE CROSSLINK AT THE N2 POSITION OF G*. MODEL OF A MALONDIALDEHYDE CROSSLINK'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Malondialdehyde (MDA), a known mutagen and suspected carcinogen, is a | + | Malondialdehyde (MDA), a known mutagen and suspected carcinogen, is a product of lipid peroxidation and byproduct of eicosanoid biosynthesis. MDA can react with DNA to generate potentially mutagenic adducts on adenine, cytosine, and particularly guanine. In addition, repair-dependent frame shift mutations in a GCGCGC region of Salmonella typhimurium hisD3052 have been attributed to formation of interstrand cross-links (Mukai, F. H. and Goldstein, B. D. Science 1976, 191, 868--869). The cross-linked species is unstable and has never been characterized but has been postulated to be a bis-imino linkage between N(2) positions of guanines. An analogous linkage has now been investigated as a stable surrogate using the self-complementary oligodeoxynucleotide sequence 5'-d(AGGCG*CCT)(2,) in which G* represents guanines linked via a trimethylene chain between N(2) positions. The solution structure, obtained by NMR spectroscopy and molecular dynamics using a simulated annealing protocol, revealed the cross-link only minimally distorts duplex structure in the region of the cross-link. The tether is accommodated by partially unwinding the duplex at the lesion site to produce a bulge and tipping the guanine residues; the two guanines and the tether attain a nearly planar conformation. This distortion did not result in significant bending of the DNA, a result which was confirmed by gel electrophoresis studies of multimers of a 21-mer duplex containing the cross-link. |
==About this Structure== | ==About this Structure== | ||
| - | 1HZ2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with TME as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1HZ2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=TME:'>TME</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HZ2 OCA]. |
==Reference== | ==Reference== | ||
Structural studies of an oligodeoxynucleotide containing a trimethylene interstrand cross-link in a 5'-(CpG) motif: model of a malondialdehyde cross-link., Dooley PA, Tsarouhtsis D, Korbel GA, Nechev LV, Shearer J, Zegar IS, Harris CM, Stone MP, Harris TM, J Am Chem Soc. 2001 Feb 28;123(8):1730-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11456774 11456774] | Structural studies of an oligodeoxynucleotide containing a trimethylene interstrand cross-link in a 5'-(CpG) motif: model of a malondialdehyde cross-link., Dooley PA, Tsarouhtsis D, Korbel GA, Nechev LV, Shearer J, Zegar IS, Harris CM, Stone MP, Harris TM, J Am Chem Soc. 2001 Feb 28;123(8):1730-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11456774 11456774] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Dooley, P | + | [[Category: Dooley, P A.]] |
| - | [[Category: Harris, C | + | [[Category: Harris, C M.]] |
| - | [[Category: Harris, T | + | [[Category: Harris, T M.]] |
| - | [[Category: Korbel, G | + | [[Category: Korbel, G A.]] |
| - | [[Category: Nechev, L | + | [[Category: Nechev, L V.]] |
[[Category: Shearer, J.]] | [[Category: Shearer, J.]] | ||
| - | [[Category: Stone, M | + | [[Category: Stone, M P.]] |
[[Category: Tsarouhtsis, D.]] | [[Category: Tsarouhtsis, D.]] | ||
| - | [[Category: Zegar, I | + | [[Category: Zegar, I S.]] |
[[Category: TME]] | [[Category: TME]] | ||
[[Category: dna duplex]] | [[Category: dna duplex]] | ||
[[Category: interstrand crosslink]] | [[Category: interstrand crosslink]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:06:16 2008'' |
Revision as of 11:06, 21 February 2008
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SOLUTION NMR STRUCTURE OF SELF-COMPLEMENTARY DUPLEX 5'-D(AGGCG*CCT)2 CONTAINING A TRIMETHYLENE CROSSLINK AT THE N2 POSITION OF G*. MODEL OF A MALONDIALDEHYDE CROSSLINK
Overview
Malondialdehyde (MDA), a known mutagen and suspected carcinogen, is a product of lipid peroxidation and byproduct of eicosanoid biosynthesis. MDA can react with DNA to generate potentially mutagenic adducts on adenine, cytosine, and particularly guanine. In addition, repair-dependent frame shift mutations in a GCGCGC region of Salmonella typhimurium hisD3052 have been attributed to formation of interstrand cross-links (Mukai, F. H. and Goldstein, B. D. Science 1976, 191, 868--869). The cross-linked species is unstable and has never been characterized but has been postulated to be a bis-imino linkage between N(2) positions of guanines. An analogous linkage has now been investigated as a stable surrogate using the self-complementary oligodeoxynucleotide sequence 5'-d(AGGCG*CCT)(2,) in which G* represents guanines linked via a trimethylene chain between N(2) positions. The solution structure, obtained by NMR spectroscopy and molecular dynamics using a simulated annealing protocol, revealed the cross-link only minimally distorts duplex structure in the region of the cross-link. The tether is accommodated by partially unwinding the duplex at the lesion site to produce a bulge and tipping the guanine residues; the two guanines and the tether attain a nearly planar conformation. This distortion did not result in significant bending of the DNA, a result which was confirmed by gel electrophoresis studies of multimers of a 21-mer duplex containing the cross-link.
About this Structure
1HZ2 is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
Structural studies of an oligodeoxynucleotide containing a trimethylene interstrand cross-link in a 5'-(CpG) motif: model of a malondialdehyde cross-link., Dooley PA, Tsarouhtsis D, Korbel GA, Nechev LV, Shearer J, Zegar IS, Harris CM, Stone MP, Harris TM, J Am Chem Soc. 2001 Feb 28;123(8):1730-9. PMID:11456774
Page seeded by OCA on Thu Feb 21 13:06:16 2008
