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

Summary for 1HZ2

• Entry DOI: 10.2210/pdb1hz2/pdb
• Descriptor: DNA (5'-D(*AP*GP*GP*CP*GP*CP*CP*T)-3'), PROPANE (2 entities in total)
• Functional Keywords: dna duplex, interstrand crosslink, dna
• Total number of polymer chains: 2
• Total formula weight: 4899.31

Authors

Dooley, P.A.,Tsarouhtsis, D.,Korbel, G.A.,Nechev, L.V.,Shearer, J.,Zegar, I.S.,Harris, C.M.,Stone, M.P.,Harris, T.M. (deposition date: 2001-01-23, release date: 2001-02-07, Last modification date: 2024-05-22)

Primary citation

Dooley, P.A.,Tsarouhtsis, D.,Korbel, G.A.,Nechev, L.V.,Shearer, J.,Zegar, I.S.,Harris, C.M.,Stone, M.P.,Harris, T.M.
Structural studies of an oligodeoxynucleotide containing a trimethylene interstrand cross-link in a 5'-(CpG) motif: model of a malondialdehyde cross-link.
J.Am.Chem.Soc., 123:1730-1739, 2001

PubMed Abstract: 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.

PubMed: 11456774
DOI: 10.1021/ja003163w

Experimental method

SOLUTION NMR