Singlet Oxygen's Response to Protein Dynamics

Singlet Oxygen's Response to Protein Dynamics
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DOI:
10.1021/ja2010708
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发表时间:
2011-05-11
影响因子:
15
通讯作者:
Ogilby, Peter R.
Ogilby, Peter R.
中科院分区:
化学1区
文献类型:
--
作者:
Jensen, Rasmus Lybech;Arnbjerg, Jacob;Ogilby, Peter R.

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单线态分子氧,O-2(a(1)Delta g),是与生物系统功能相关的各种过程的中间体,包括导致细胞死亡的事件。许多这些过程涉及单线态氧和给定蛋白质之间的反应。公认的是,蛋白质的行为可以在与单线态氧反应时改变,这是结构改变和/或活性位点的直接化学修饰的结果。然而,匡威,人们考虑如何通过蛋白质结构的变化来改变单线态氧的行为,却很少受到关注。在这份报告中,我们使用各种蛋白质,以证明如何由蛋白质的单线态氧去除速率常数响应于(a)蛋白质变性,(B)大分子拥挤的蛋白质,(c)配体结合的蛋白质,和(d)聚合的蛋白质。从一个角度来看,数据显示单线态氧去除的动力学可用于监测蛋白质动力学。然而,最重要的是,这些数据表明,蛋白质结构的变化,无论是揭示或掩盖一个给定的氨基酸残基可以有一个可测量的影响的整体速率常数单线态氧去除,这反过来,可以有分歧单线态氧介导的细胞内事件,扰乱细胞功能。
Singlet molecular oxygen, O-2(a(1)Delta g), is an intermediate in a variety of processes pertinent to the function of biological systems, including events that result in cell death. Many of these processes involve a reaction between singlet oxygen and a given protein. It is acknowledged that the behavior of a protein can change upon reaction with singlet oxygen, as a result of a structural alteration and/or a direct chemical modification of an active site. However, the converse, where one considers how the behavior of singlet oxygen can be altered by changes in protein structure, has received little attention. In this report, we use a variety of proteins to demonstrate how the rate constant for singlet oxygen removal by a protein responds to (a) protein denaturation, (b) macromolecular crowding of the protein, (c) ligand binding by the protein, and (d) polymerization of the protein. From one perspective, the data show that the kinetics of singlet oxygen removal can be used to monitor protein dynamics. Most importantly, however, the data indicate that protein structural changes that either reveal or cloak a given amino add residue can have a measurable effect on the overall rate constant for singlet oxygen removal which, in turn, can have ramifications for singlet-oxygen-mediated intracellular events that perturb cell function.