Cuniasse P, Sowers L C, Eritja R, Kaplan B, Goodman M F, Cognet J A, LeBret M, Guschlbauer W, Fazakerley G V
Département de Biologie, Centre d'Etudes Nucléarie de Saclay, Gif-sur-Yvette, France.
Nucleic Acids Res. 1987 Oct 12;15(19):8003-22. doi: 10.1093/nar/15.19.8003.
We have determined the three-dimensional structure of a non-selfcomplementary nonanucleotide duplex which contains an abasic (apyrimidinic) site in the centre, i.e. a deoxyribose residue opposite an adenosine. The majority of the base and sugar proton resonances were assigned by NOESY, COSY and 2DQF spectra in D2O and H2O. We have measured the initial slope of buildup of NOEs in NOESY spectra at very short mixing times (25 to 50 ms), and from these were able to establish interproton distances for the central part of the duplex. We propose a different strategy for proton-proton distance determinations which takes into account the observed variations in correlation times for particular proton-proton vectors. A set of 31 measured interproton distances was incorporated into the refinement of the oligonucleotide structure by molecular mechanics calculations. Two structures were obtained which retain all aspects of a classical B DNA in which the unpaired adenine and the abasic deoxyribose lie inside the helix. We observe that the non-hydrogen bonded adenine is held well in the helix, the Tm of this base being the same as that of the A.T base pairs in the same duplex.
我们已经确定了一种非自我互补九核苷酸双链体的三维结构,该双链体在中心位置含有一个无碱基(无嘧啶)位点,即与一个腺苷相对的脱氧核糖残基。在D2O和H2O中,通过NOESY、COSY和二维量子滤波(2DQF)谱对大多数碱基和糖质子共振进行了归属。我们在非常短的混合时间(25至50毫秒)下测量了NOESY谱中NOE积累的初始斜率,并据此确定了双链体中心部分的质子间距离。我们提出了一种不同的质子-质子距离测定策略,该策略考虑了特定质子-质子向量相关时间的观测变化。通过分子力学计算,将一组31个测量的质子间距离纳入寡核苷酸结构的精修中。得到了两种结构,它们保留了经典B型DNA的所有特征,其中未配对的腺嘌呤和无碱基脱氧核糖位于螺旋内部。我们观察到,未形成氢键的腺嘌呤在螺旋中保持良好,该碱基的熔解温度与同一双链体中A·T碱基对的熔解温度相同。