Internal degrees of freedom, structural motifs, and conformational energetics of the 5'-deoxyadenosyl radical: implications for function in adenosylcobalamin-dependent enzymes. A computational study.
Internal degrees of freedom, structural motifs, and conformational energetics of the 5'-deoxyadenosyl radical: implications for function in adenosylcobalamin-dependent enzymes. A computational study.
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5-脱氧腺苷自由基的内部自由度、结构基序和构象能量学：对腺苷钴胺依赖性酶功能的影响。
DOI：
10.1021/ja028393k
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发表时间：
2003
影响因子：
15
通讯作者：
Morokuma,Keiji
中科院分区：
文献类型：
--
作者：
Khoroshun,DmitryV;Warncke,Kurt;Ke,Shyue-Chu;Musaev,DjamaladdinG;Morokuma,Keiji
使用具有 6-31G(d) 和 6-31++G(d,p) 基组的密度泛函和二阶 Møller−Plesset 微扰理论探索气相中游离 5'-脱氧腺苷自由基的势能表面，并根据吸引和排斥相互作用进行解释。发现 5’,8-环化反应放热约 20 kcal/mol，但动力学上不利；对于大多数开放异构体之间的转化，最低环化过渡态 (TS) 比最高 TS 高约 7 kcal/mol。在开放异构体中，两个能量上最重要的吸引相互作用是 (a) 2'-OH 基团和 N3 腺嘌呤中心之间的氢键以及 (b) 2'-OH 和 3'-OH 基团之间的氢键。在一定范围内，围绕 C1'−N9 糖基键的相对核糖−腺嘌呤旋转使能量变化高达 10−15 kcal/mol，其根源在于 (i) 排斥性 2'-H···H−C8 和 O1'···N3 和 (ii) 吸引性 2'-OH···N3 核糖−腺嘌呤相互作用。糖基旋转和 Co−C 键断裂之间假设的协同作用可能有助于实验确定酶结合腺苷钴胺素中 Co−C 键的不稳定。计算结果与 C1'−N9 糖基键的旋转并不不一致，C1'−N9 糖基键是辅酶 B12 依赖性酶中长程自由基迁移的主坐标。蛋白质环境对此处报告的模型系统结果的影响仍然是一个悬而未决的问题。
The potential energy surface of the free 5‘-deoxyadenosyl radical in the gas phase is explored using density functional and second-order Møller−Plesset perturbation theories with 6-31G(d) and 6-31++G(d,p) basis sets and interpreted in terms of attractive and repulsive interactions. The 5‘,8-cyclization is found to be exothermic by ∼20 kcal/mol but kinetically unfavorable; the lowest cyclization transition state (TS) lies about 7 kcal/mol higher than the highest TS for conversion between most of the open isomers. In open isomers, the two energetically most important attractive interactions are the hydrogen bonds (a) between the 2‘-OH group and the N3 adenine center and (b) between the 2‘-OH and 3‘-OH groups. The relative ribose−adenine rotation about the C1‘−N9 glycosyl bond in a certain range changes the energy by as much as 10−15 kcal/mol, the origin being (i) the repulsive 2‘-H···H−C8 and O1‘···N3 and (ii) the attractive 2‘-OH···N3 ribose−adenine interactions. The hypothetical synergy between the glycosyl rotation and the Co−C bond scission may contribute to the experimentally established labilization of the Co−C bond in enzyme-bound adenosylcobalamin. The computational results are not inconsistent with the rotation about the C1‘−N9 glycosyl bond being the principal coordinate for long-range radical migration in coenzyme B12-dependent enzymes. The effect of the protein environment on the model system results reported here remains an open question.