1hz2

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[[Image:1hz2.gif|left|200px]]
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[[Image:1hz2.png|left|200px]]
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{{STRUCTURE_1hz2| PDB=1hz2 | SCENE= }}
{{STRUCTURE_1hz2| PDB=1hz2 | SCENE= }}
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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'''
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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===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 11456774 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11456774}}
==About this Structure==
==About this Structure==
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Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HZ2 OCA].
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Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HZ2 OCA].
==Reference==
==Reference==
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[[Category: Dna duplex]]
[[Category: Dna duplex]]
[[Category: Interstrand crosslink]]
[[Category: Interstrand crosslink]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 10:09:34 2008''

Revision as of 07:09, 1 July 2008

Image:1hz2.png

Template:STRUCTURE 1hz2

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

Template:ABSTRACT PUBMED 11456774

About this Structure

Full experimental 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

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