D-Amino acids in protein: The mirror of life as a molecular index of aging
D-Amino acids in protein: The mirror of life as a molecular index of aging
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DOI：
10.1016/j.bbapap.2018.03.001
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发表时间：
2018-07-01
影响因子：
3.2
通讯作者：
Sakaue, Hiroaki
中科院分区：
文献类型：
--
作者：
Fujii, Noriko;Takata, Takumi;Sakaue, Hiroaki
蛋白质仅由 L-氨基酸组成。然而，在老年人中，在眼晶状体、大脑以及其他组织中发现了 D-天冬氨酸 (D-Asp) 残留物。 D-Asp 的存在可能会改变蛋白质的高级结构，进而可能在白内障和阿尔茨海默病等与年龄相关的疾病中发挥作用。 D-Asp 由敏感蛋白质中的 Asp 残基自发外消旋产生。在老化过程中，蛋白质中的天然 L α-Asp 残基通过琥珀酰亚胺基中间体非酶促异构化为 L-β-、D-α- 和 D-β- 异构体。这种异构化不是均匀发生的，而是发生在由于其序列或结构背景而容易发生异构化的特定残基处。因此，有必要确定易感蛋白中每个单独的天冬氨酸残基的性质。最近，描述了一种基于 LC-MS/MS 的新方法，用于分析特定蛋白质位点的 Asp 异构化。在这篇综述中，我们首先表明蛋白质中氨基酸的同手性在整个生命过程中都无法得到保证。然后，我们描述了蛋白质结合 D-氨基酸分析新方法的开发，并讨论了 D-Asp 对蛋白质结构和功能的负面影响。
Proteins are composed exclusively of L-amino acids. Among elderly individuals, however, D-aspartic acid (D-Asp) residues have been found in eye lens and brain, as well as in other tissues. The presence of D-Asp may change the higher-order structure of a protein, which in turn may have a role in age-related disorders such as cataract and Alzheimer's disease. D-Asp results from the spontaneous racemization of Asp residues in susceptible proteins. During aging, natural L alpha-Asp residues in proteins are non-enzymatically isomerized via a succinimidyl intermediate to L-beta-, D-alpha- and D-beta-isomers. This isomerization does not happen uniformly, but instead occurs at specific residues that are susceptible to isomerization due to their sequence or structural context. Thus, it is necessary to establish the nature of each individual Asp residue in susceptible proteins. Recently, a new method based on LC-MS/MS for the analysis of Asp isomerization at specific protein sites has been described. In this review, we first show that the homochirality of amino acids in proteins is not guaranteed throughout life. We then describe the development of a new method for protein-bound D-amino acid analysis, and discuss the negative influence that D-Asp has on protein structure and function.