Factors determining the selectivity of protein tyrosine nitration
Factors determining the selectivity of protein tyrosine nitration
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DOI：
10.1006/abbi.1999.1480
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发表时间：
1999-11-15
影响因子：
3.9
通讯作者：
Ischiropoulos, H
中科院分区：
文献类型：
--
作者：
Souza, JM;Daikhin, E;Ischiropoulos, H
酪氨酸硝化是蛋白质与硝化剂反应产生的共价翻译后修饰。蛋白质硝化似乎是一个选择性的过程，因为不是所有蛋白质中的酪氨酸残基或所有蛋白质在体内被硝化。为了研究可能决定蛋白质酪氨酸硝化生物选择性的因素，我们开发了一个体外模型，该模型由三种大小相似但三维结构和酪氨酸含量不同的蛋白质组成。核糖核酸酶A暴露在推定的体内硝化剂显示优先硝化酪氨酸残基Y-115。酪氨酸残基Y-23和较小程度的残基Y-20在溶菌酶中优先硝化，而酪氨酸Y-102是磷脂酶A中唯一被硝化修饰的残基（2）。酪氨酸Y-115是核糖核酸酶A暴露于不同硝化剂后通过硝化修饰的残基：化学合成的过氧亚硝酸盐、一氧化氮和由SIN-1或髓过氧化物酶（MPO）/H2 O2在碳酸氢盐/CO2存在下产生的超氧化物加上亚硝酸盐（NO2-）。硝化剂的性质部分地决定了在所有三种蛋白质的混合物中主要通过硝化改性的蛋白质。核糖核酸酶A在暴露于MPO/H2 O2/NO2-时优先硝化，而磷脂酶A（2）在暴露于过氧亚硝酸盐时是硝化的主要靶。这些数据还表明，暴露的芳香环的蛋白质的表面上，酪氨酸的位置上的一个环结构，以及它的协会与邻近的负电荷是一些因素，确定酪氨酸硝化在蛋白质的选择性。(C)北京：科学出版社.
Tyrosine nitration is a covalent posttranslational protein modification derived from the reaction of proteins with nitrating agents. Protein nitration appears to be a selective process since not all tyrosine residues in proteins or all proteins are nitrated in vivo. To investigate factors that may determine the biological selectivity of protein tyrosine nitration, we developed an in vitro model consisting of three proteins with similar size but different three-dimensional structure and tyrosine content. Exposure of ribonuclease A to putative in vivo nitrating agents revealed preferential nitration of tyrosine residue Y-115. Tyrosine residue Y-23 and to a lesser extent residue Y-20 were preferentially ;nitrated in lysozyme, whereas tyrosine Y-102 was the only residue modified by nitration in phospholipase A(2). Tyrosine Y-115 was the residue modified by nitration after exposure of ribonuclease A to different nitrating agents: chemically synthesized peroxynitrite, nitric oxide, and superoxide generated by SIN-1 or myeloperoxidase (MPO)/H2O2 plus nitrite (NO2-) in the presence of bicarbonate/CO2. The nature of the nitrating agent determined in part the protein that would be predominantly modified by nitration in a mixture of all three proteins. Ribonuclease A was preferentially nitrated upon exposure to MPO/H2O2/NO2-, whereas phospholipase A(2) was the primary target for nitration upon exposure to peroxynitrite. The data also suggest that the exposure of the aromatic ring to the surface of the protein, the location of the tyrosine on a loop structure, and its association with a neighboring negative charge are some of the factors determining the selectivity of tyrosine nitration In proteins. (C) 1999 Academic Press.