Review of tyrosine and lysine as new motifs for organophosphate binding to proteins that have no active site serine
Review of tyrosine and lysine as new motifs for organophosphate binding to proteins that have no active site serine
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DOI：
10.1016/j.cbi.2010.03.002
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发表时间：
2010-09-06
影响因子：
5.1
通讯作者：
Schopfer, Lawrence M.
中科院分区：
文献类型：
--
作者：
Lockridge, Oksana;Schopfer, Lawrence M.
有机磷试剂(OP)与酶结合的公认靶点是Gly X Ser X Gly共有序列中的活性部位丝氨酸。通过使用质谱学对OP标记的多肽进行碎片处理，已经鉴定出新的基序。已发现OP可以与蛋白质中没有丝氨酸活性部位的酪氨酸和赖氨酸形成共价键。OP-酪氨酸键是稳定的，不会像OP-丝氨酸那样衰退。通过使用质谱仪检测人和动物血浆中OP标记的白蛋白，OP与酪氨酸结合的信息已被应用于OP暴露的诊断。预计新的OP结合基序将有助于寻找低剂量OP毒性的机制。据推测，参与轴突运输的蛋白质，特别是其功能依赖于可逆磷酸化的蛋白质，是OP诱导的神经退行性变的主要候选者。通过确定逆转OP与酪氨酸结合的方法，可以开发神经退行性疾病的治疗方法。(C)2010爱思唯尔爱尔兰有限公司。保留所有权利。
The accepted target for organophosphorus agent (OP) binding to enzymes is the active site serine in the consensus sequence Gly X Ser X Gly. New motifs have been identified by using mass spectrometry to fragment OP-labeled peptides. It has been found that OP can make covalent bonds with tyrosine and lysine in proteins that have no active site serine. The OP-tyrosine bond is stable, and does not undergo the decay seen with OP-serine. Information on OP binding to tyrosine has been applied to diagnosis of OP exposure, through the use of mass spectrometry to detect OP-labeled albumin in human and animal plasma. It is expected that the new OP binding motif will aid in the search for a mechanism of low dose OP toxicity. It is hypothesized that proteins involved in axonal transport, especially proteins whose function depends on reversible phosphorylation, are prime candidates fora role in OP-induced neurodegeneration. Treatment of neurodegenerative disorders could be developed by identifying methods to reverse OP binding to tyrosine. (C) 2010 Elsevier Ireland Ltd. All rights reserved.