223D

DIRECT OBSERVATION OF TWO BASE-PAIRING MODES OF A CYTOSINE-THYMINE ANALOGUE WITH GUANINE IN A DNA Z-FORM DUPLEX: SIGNIFICANCE FOR BASE ANALOGUE MUTAGENESIS

Summary for 223D

• Entry DOI: 10.2210/pdb223d/pdb
• Descriptor: DNA (5'-D(*CP*GP*CP*GP*(C46)P*G)-3') (2 entities in total)
• Functional Keywords: z-dna, double helix, modified, dna
• Total number of polymer chains: 2
• Total formula weight: 3704.48

Authors

Moore, M.H.,Van Meervelt, L.,Salisbury, S.A.,Kong Thoo Lin, P.,Brown, D.M. (deposition date: 1995-08-01, release date: 1995-12-09, Last modification date: 2024-04-03)

Primary citation

Moore, M.H.,Van Meervelt, L.,Salisbury, S.A.,Lin, P.K.,Brown, D.M.
Direct observation of two base-pairing modes of a cytosine-thymine analogue with guanine in a DNA Z-form duplex: significance for base analogue mutagenesis.
J.Mol.Biol., 251:665-673, 1995

PubMed Abstract: The pyrimidine nucleobase analogue 6H,8H-3,4-dihydropyrimido[4,5-c]- [1,2]oxazin-7-one (P) is a mimic both of cytosine and thymine, since it can form stable hydrogen-bonded base-pairs with either guanine or adenine. To investigate the geometric properties of pairing with guanine in a DNA double helix, the structure of d(CGCGPG)2 has been determined by single crystal X-ray analysis. The oligonucleotide crystallised as a left-handed Z-DNA duplex in the orthorhombic space group P2(1)2(1)2(1) with cell dimensions a = 18.23 A, b = 30.63 A, c = 43.78 A. Refinement using NUCLSQ with 51 water molecules included in the final model converged at R = 0.179 (Rw = 0.159) for 2798 reflections (F > 2 sigma (F)) in the range 8 A to 1.7 A. Remarkably, the two P.G pairs in the hexamer duplex are different: Watson-Crick and wobble types separately illustrate both cytosine-like and thymine-like behaviour. The result suggests that mutagenesis experiments involving P and other analogues which display pronounced base-pairing ambivalence can be used to examine the structural basis of substrate discrimination by polymerases that is essential to accurate genetic replication.

PubMed: 7666418
DOI: 10.1006/jmbi.1995.0463

Experimental method

X-RAY DIFFRACTION (1.7 Å)