Conformational determinants of structures in stereoisomeric cis-opened anti-benzo[a]pyrene diol epoxide adducts to adenine in DNA.
Conformational determinants of structures in stereoisomeric cis-opened anti-benzo[a]pyrene diol epoxide adducts to adenine in DNA.
复制标题
DNA 中腺嘌呤立体异构顺式开环抗苯并[a]芘二醇环氧化物加合物结构的构象决定因素。
DOI：
10.1021/tx000094q
复制
发表时间：
2000
影响因子：
4.1
通讯作者：
Broyde,S
中科院分区：
文献类型：
--
作者：
Tan,J;Geacintov,NE;Broyde,S
作为理解（+）-和（−）-顺式-和反式-反式-[BP]-N2-dG和-N6-dA加合物所采用的各种结构基序的起源的全面努力的一部分，目的是有助于阐明结构-功能关系，我们目前的结果，我们全面的计算研究的C10 R（+）-顺式-和C10 S（-）-顺式-反-[BP]-N6-dA加合物的核苷水平。我们已经调查了这两个加合物的势能面，通过系统地改变，在5°的间隔组合，在每个加合物中的构象柔性的三个关键扭转角决定因素（χ，χ '，和χ'），创建373 248个结构，并评估它们的能量。这使我们能够映射每个加合物的整个势能面，并描绘出低能区。能量图在（+）/（−）加合物对中具有对称关系。图中的这种对称性源于两种加合物中苄基环的镜像构型，这在核苷水平上产生C10 R和C10 Sadducts中BP残基的相反取向。这些相反的取向是由碱基和BP部分之间的主要空间位阻引起的，当（+）立体异构体旋转到（-）立体异构体所有利于的构象时，该主要空间位阻会阻碍（-）立体异构体的旋转，反之亦然。此外，这种空间位阻表现在核苷水平上的双链体DNA水平上的结构，占观察到的相反方向在高分辨率NMR研究C10 R/C10 S加合物对。
As part of a comprehensive effort to understand the origins of the variety of structural motifs adopted by (+)- and (−)-cis- andtrans-anti-[BP]-N2-dG and -N6-dA adducts, with the goal of contributing to the elucidation of the structure−function relationship, we present results of our comprehensive computational investigation of the C10R(+)-cis- and C10S(−)-cis-anti-[BP]-N6-dA adducts on the nucleoside level. We have surveyed the potential energy surface of these two adducts by varying systematically, at 5° intervals in combination, the three key torsion angle determinants of conformational flexibility (χ, α‘, and β‘) in each adduct, creating 373 248 structures, and evaluating each of their energies. This has permitted us to map the entire potential energy surface of each adduct and to delineate the low-energy regions. The energy maps possess a symmetric relationship in the (+)/(−) adduct pair. This symmetry in the maps stems from the mirror image configuration of the benzylic rings in the two adducts, which produces opposite orientations of the BP residues in the C10Rand C10Sadducts on the nucleoside level. These opposite orientations result from primary steric hindrance between the base and the BP moiety which ensues when a (+) stereoisomer is rotated to the conformation favored by the (−) stereoisomer, and vice versa. Moreover, this steric hindrance manifested on the nucleoside level governs the structure on the duplex DNA level, accounting for observed opposite orientations in high-resolution NMR studies of C10R/C10Sadduct pairs.