1XCI

Mispair Aligned N3T-Butyl-N3T Interstrand Crosslink

Summary for 1XCI

• Entry DOI: 10.2210/pdb1xci/pdb
• Descriptor: 5'-D(*CP*GP*AP*AP*AP*(TTM)P*TP*TP*TP*CP*G)-3' (1 entity in total)
• Functional Keywords: interstrand cross-link, double helix, dna
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 6752.53

Authors

da Silva, M.W.,Bierbryer, R.G.,Wilds, C.J.,Noronha, A.M.,Colvin, O.M.,Miller, P.S.,Gamcsik, M.P. (deposition date: 2004-09-02, release date: 2005-08-16, Last modification date: 2024-05-01)

Primary citation

da Silva, M.W.,Bierbryer, R.G.,Wilds, C.J.,Noronha, A.M.,Colvin, O.M.,Miller, P.S.,Gamcsik, M.P.
Intrastrand base-stacking buttresses widening of major groove in interstrand cross-linked B-DNA.
Bioorg.Med.Chem., 13:4580-4587, 2005

PubMed Abstract: The introduction of a covalent interstrand cross-link induces changes in the intrinsic structure and deformability of the DNA helix that are recognized by elements of the DNA repair apparatus. In this context, the solution structure of the undecamer d(CGAAAT*TTTCG)2, where T* represents a N3T-butyl-N3T interstrand cross-link, was determined using molecular dynamics calculations restrained by NOE and dihedral angle data obtained from NMR spectroscopy. The structure of this cross-linked undecamer shows dramatic widening of the major groove of the B-DNA stem without disruption of Watson-Crick base pairing. This change in tertiary structure illustrates the cumulative effect of cooperativity in intrastrand base stacking of an A-tract of three adenines. Further, it is the direct result from the imposition of geometric angular constraints by the cross-link chain on an ApT* and T*pT steps in the segment AAAT*T. The widening of the major groove is due to the dominant contribution of base stacking to the stability of the ApT compared to the TpT step suggesting that the latter is more deformable within a DNA stem. Compared to earlier structures of ethyl cross-linked oligonucleotides, this unique perturbation induced by the butyl moiety offers a new probe for systematic studies of DNA repair mechanisms.

PubMed: 15953553
DOI: 10.1016/j.bmc.2005.03.032

Experimental method

SOLUTION NMR