1au5
From Proteopedia
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SOLUTION STRUCTURE OF INTRASTRAND CISPLATIN-CROSSLINKED DNA OCTAMER D(CCTG*G*TCC):D(GGACCAGG), NMR, MINIMIZED AVERAGE STRUCTURE
Overview
The anticancer platinum compound cis-Pt(NH3)2Cl2 (cisplatin) forms, covalent cross-linked adducts with DNA, with the intrastrand didentate, adduct between two adjacent guanines being the major product. The platinum, atom is coordinated at the N7 positions of adjacent guanines. The duplex, consisting of d(CCTG*G*TCC) and its complement d(GGACCAGG), where G*G*, stands for the cisplatin cross-linked lesion site, has been analyzed by, 1D- and 2D-NMR spectroscopy and its structure solved by the NOE-restrained, refinement procedure with the aim to understand the structural distortion, associated with the lesion. The refined duplex is unwound (approximately, -21 degrees) and kinked (approximately 58 degrees) toward the major groove, at the G*G* site, and the minor groove is significantly widened. The, deoxyriboses of the G4* and G5* nucleotides are of the N-type (C3'-endo), and S-type (C2'-endo) conformations, respectively. The two guanine bases, adopt the R-configuration (the alpha/beta angles being 112 degrees/290, degrees, respectively), such that the G5*H8 proton (upfield at 8.19 ppm), senses the ring current shielding effect of the G4* base (G4*H8 at 8.76, ppm). The G4*.C13 base pair is perturbed significantly, consistent with, the lack of detection of its imino proton. The intrastrand Pt-G*pG*, cross-link is metastable in the present DNA duplex. The molecule is slowly, converted into a more stable interstrand didentate adduct (between G4 and, G9) promoted by the presence of the nucleophilic chloride ion.(ABSTRACT, TRUNCATED AT 250 WORDS)
About this Structure
1AU5 is a Protein complex structure of sequences from [1] with CPT as ligand. Full crystallographic information is available from OCA.
Reference
Structure and isomerization of an intrastrand cisplatin-cross-linked octamer DNA duplex by NMR analysis., Yang D, van Boom SS, Reedijk J, van Boom JH, Wang AH, Biochemistry. 1995 Oct 3;34(39):12912-20. PMID:7548048
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