Electrostatic activation of Escherichia coli methionine repressor.
Electrostatic activation of Escherichia coli methionine repressor.
复制标题
大肠杆菌蛋氨酸阻遏物的静电激活。
DOI：
10.1016/s0969-2126(00)00032-0
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Phillips,SE
中科院分区：
文献类型：
--
作者：
Phillips,K;Phillips,SE
背景：大肠杆菌的三维结构。蛋氨酸抑制子(Metrepressor)相对不受辅阻遏子S-腺苷甲硫氨酸(SAM)和操纵子DNA结合的干扰。带正电的辅阻遏子结合到远离DNA结合位点的抑制子上的位点，尽管没有诱导结构变化，但能够将与操纵子DNA的亲和力提高1000倍。结果用Delphi程序计算了抑制子及其复合体的静电势，得到了与抑制子及其复合体的静电势，得到了与抑制子激活的静电模型一致的结果。来自辅阻遏子的正电势通过阻遏子-操纵子复合体传播，并且在隐藏在蛋白质-DNA界面的DNA磷酸基团中具有重要意义。计算的SAM和两个密切相关类似物的静电相互作用能的排序与相应的阻遏因子-操纵子亲和作用的实验测量结果一致。结论阻遏因子-操纵子复合体中结合辅阻遏子和操纵子磷酸基团之间的长程(>；10？)静电相互作用可能足以解释阻遏因子的激活。因此，阻遏因子可能是一种静电触发的遗传开关。
BackgroundThe three-dimensional structure of theEscherichia. colimethionine repressor (metrepressor) is relatively unperturbed by the binding of its corepressor,S-adenosylmethionine (SAM), and of operator DNA. The positively charged corepressor binds to sites on the repressor remote from the DNA-binding site, and despite the lack of induced structural change is able to raise the affinity for operator DNA by a factor of up to 1000. Neutral corepressor analogues also bind to the repressor, but do not increase operator affinity.These observations suggest that the corepressor effect may be electrostatic.ResultsUsing the program DELPHI, we have calculated electrostatic potentials for the repressor and its complexes, and have obtained results consistent with an electrostatic model for repressor activation. The positive potential originating from the corepressor is propagated through the repressor–operator complex, and is significant at DNA phosphate groups buried in the protein–DNA interface. The rank order of calculated electrostatic interaction energies for complexes with SAM, and two closely- related analogues, is in agreement with experimental measurements of the corresponding repressor–operator affinities.ConclusionsLong-range ( > 10 å) electrostatic interactions between bound corepressor and operator phosphate groups in the repressor–operator complex may be sufficient to explain repressor activation.Metrepressor could, therefore, be an electrostatically triggered genetic switch.