Yuki M, Grukhin V, Lee C S, Haworth I S
Department of Pharmaceutical Sciences, University of Southern California, Los Angeles 90033, USA.
Arch Biochem Biophys. 1996 Jan 1;325(1):39-46. doi: 10.1006/abbi.1996.0005.
The DNA binding of spermine has been studied using experimental and computational approaches. Spermine blocks 5'-GC interstrand crosslinking by 2,5-diaziridinylbenzoquinone in the oligonucleotide duplex 5'-CTTCCAAGATGCATCAGATG 5'-CATCTGATGCATCTTGGAAG (where the underlined nucleotide bases represent the crosslinking site). Molecular dynamics simulations suggest that this is a result of preferential spermine binding at the 5'-GC major groove site of the oligonucleotide. A further simulation with a GC-alternating sequence shows a similar preference for the 5'-GC step. In a simulation including multiple spermine molecules, occupation of alternate 5'-GC steps occurred. From this, we deduced a mechanism for the experimentally observed cooperativity of spermine binding to poly(dGdC)2.
已使用实验和计算方法研究了精胺与DNA的结合。精胺可阻止2,5-二氮杂环丁烷基苯醌在寡核苷酸双链体5'-CTTCCAAGATGCATCAGATG 5'-CATCTGATGCATCTTGGAAG（其中下划线的核苷酸碱基代表交联位点）中引发的5'-GC链间交联。分子动力学模拟表明，这是精胺优先结合于寡核苷酸5'-GC大沟位点的结果。对GC交替序列的进一步模拟显示出对5'-GC步的类似偏好。在包含多个精胺分子的模拟中，出现了交替占据5'-GC步的情况。据此，我们推导了精胺与聚（dGdC）2结合时实验观察到的协同作用机制。
