1LUH

SOLUTION NMR STRUCTURE OF SELF-COMPLIMENTARY DUPLEX 5'-D(TCCG*CGGA)2 CONTAINING A TRIMETHYLENE CROSSLINK AT THE N2 POSITION OF G*

Summary for 1LUH

• Entry DOI: 10.2210/pdb1luh/pdb
• Descriptor: 5'-D(*TP*CP*CP*(TME)GP*CP*GP*GP*A)-3', PROPANE (2 entities in total)
• Functional Keywords: dna duplex, guanine n2-guanine n2 interstrand crosslink, dna
• Total number of polymer chains: 2
• Total formula weight: 4899.31

Authors

Dooley, P.D.,Zhang, M.,Korbel, G.A.,Nechev, L.V.,Harris, C.M.,Stone, M.P.,Harris, T.M. (deposition date: 2002-05-22, release date: 2003-02-11, Last modification date: 2024-05-22)

Primary citation

Dooley, P.D.,Zhang, M.,Korbel, G.A.,Nechev, L.V.,Harris, C.M.,Stone, M.P.,Harris, T.M.
NMR Determination of the Conformation of a Trimethylene Interstrand Cross-Link in an Oligodeoxynucleotide Duplex Containing a 5'-d(GpC) Motif
J.AM.CHEM.SOC., 125:62-72, 2003

PubMed Abstract: Malondialdehyde interstrand cross-links in DNA show strong preference for 5'-d(CpG) sequences. The cross-links are unstable and a trimethylene cross-link has been used as a surrogate for structural studies. A previous structural study of the 5'-d(CpG) cross-link in the sequence 5'-d(AGGCGCCT), where G is the modified nucleotide, by NMR spectroscopy and molecular dynamics using a simulated annealing protocol showed the guanine residues and the tether lay approximately in a plane such that the trimethylene tether and probably the malondialdehyde tether, as well, could be accommodated without major disruptions of duplex structure [Dooley et al. J. Am Chem. Soc. 2001, 123, 1730-1739]. The trimethylene cross-link has now been studied in a GpC motif using the reverse sequence. The structure lacks the planarity seen with the 5'-d(CpG) sequence and is skewed about the trimethylene cross-link. Melting studies indicate that the trimethylene cross-link is thermodynamically less stable in the GpC motif than in the 5-d(CpG). Furthermore, lack of planarity of the GpC cross-link precludes making an isosteric replacement of the trimethylene tether by malondialdehyde. A similar argument can be used to explain the 5'-d(CpG) preference for interchain cross-linking by acrolein.

PubMed: 12515507
DOI: 10.1021/ja0207798

Experimental method

SOLUTION NMR