1hz2
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(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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Revision as of 01:10, 25 November 2007
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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 TME 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
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