Aishima Jun, Gitti Rossitza K, Noah Joyce E, Gan Hin Hark, Schlick Tamar, Wolberger Cynthia
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA.
Nucleic Acids Res. 2002 Dec 1;30(23):5244-52. doi: 10.1093/nar/gkf661.
Hoogsteen base pairs within duplex DNA typically are only observed in regions containing significant distortion or near sites of drug intercalation. We report here the observation of a Hoogsteen base pair embedded within undistorted, unmodified B-DNA. The Hoogsteen base pair, consisting of a syn adenine base paired with an anti thymine base, is found in the 2.1 A resolution structure of the MATalpha2 homeodomain bound to DNA in a region where a specifically and a non-specifically bound homeodomain contact overlapping sites. NMR studies of the free DNA show no evidence of Hoogsteen base pair formation, suggesting that protein binding favors the transition from a Watson-Crick to a Hoogsteen base pair. Molecular dynamics simulations of the homeodomain-DNA complex support a role for the non-specifically bound protein in favoring Hoogsteen base pair formation. The presence of a Hoogsteen base pair in the crystal structure of a protein-DNA complex raises the possibility that Hoogsteen base pairs could occur within duplex DNA and play a hitherto unrecognized role in transcription, replication and other cellular processes.
双链DNA中的Hoogsteen碱基对通常仅在含有明显扭曲的区域或药物嵌入位点附近被观察到。我们在此报告在未扭曲、未修饰的B-DNA中嵌入的一个Hoogsteen碱基对的观察结果。这个由一个顺式腺嘌呤碱基与一个反式胸腺嘧啶碱基配对组成的Hoogsteen碱基对，存在于MATalpha2同源结构域与DNA结合的2.1埃分辨率结构中，该区域有一个特异性结合和一个非特异性结合的同源结构域接触重叠位点。对游离DNA的核磁共振研究没有显示出Hoogsteen碱基对形成的证据，这表明蛋白质结合有利于从沃森-克里克碱基对向Hoogsteen碱基对的转变。同源结构域-DNA复合物的分子动力学模拟支持非特异性结合蛋白在促进Hoogsteen碱基对形成中所起的作用。蛋白质-DNA复合物晶体结构中存在Hoogsteen碱基对，这增加了Hoogsteen碱基对可能出现在双链DNA中并在转录、复制和其他细胞过程中发挥迄今未被认识的作用的可能性。
