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New insight into enzymatic hydrolysis of peptides with site-specific amino acid d-isomerization
Bioorganic Chemistry ( IF 5.1 ) Pub Date : 2020-10-17 , DOI: 10.1016/j.bioorg.2020.104389
Liang Yan , Yongqi Ke , Yuhe Kan , Dao Lin , Jingkui Yang , Yujian He , Li Wu

The isomerization of l-amino acids in peptides and proteins into d-configuration under physiological conditions would affect the physiological dysfunction and caused protein conformational diseases. The presence of d-amino acids might change the higher-order structure of proteins and triggered abnormal aggregation. In order to better understand this phenomenon and promote degradation, we systematically studied the enzymatic hydrolysis of a series of peptides obtained by replacing l-amino acids in different positions of template peptide KYNETWRSED with d-amino acids under the action of Protease K. The results showed that, compared with normal peptide, isomerization of different amino acids had different effects on the anti-enzymatic hydrolysis of the peptides, especially d-tryptophan at position 6, which significantly inhibited enzymatic hydrolysis. The analysis of the peptide cleavage site revealed that the efficiency of enzymatic hydrolysis mainly depended on the isomerization of the amino acids at a specific site of the peptide cleavage. Further studies showed that the enzymatic hydrolysis of substrates could be facilitated by optimized reaction conditions such as temperature, pH, addition of metal ions, and change of buffer. In this way the accumulation of disease-associated d-amino acid containing polypeptides/proteins could be prevented.



中文翻译:

具有位点特异性氨基酸d-异构化的酶促水解肽的新见解

的异构化-氨基中的肽和蛋白质的酸成d生理条件下构型会影响生理功能障碍而引起的蛋白质构象疾病。d-氨基酸的存在可能会改变蛋白质的高级结构并引发异常聚集。为了更好地理解这种现象并促进降解,我们系统地研究了通过用d取代模板肽KYNETWRSED不同位置上的l-氨基酸获得的一系列肽的酶促水解。-氨基酸在蛋白酶K的作用下。结果表明,与正常肽相比,不同氨基酸的异构化对肽的抗酶水解作用不同,尤其是6位的d-色氨酸,显着抑制了酶的水解。水解。肽切割位点的分析表明,酶促水解的效率主要取决于肽切割特定位点上氨基酸的异构化。进一步的研究表明,可以通过优化反应条件(例如温度,pH,添加金属离子和改变缓冲液)来促进底物的酶促水解。这样,与疾病相关的d的积累可以防止含有氨基酸的多肽/蛋白质。

更新日期:2020-10-30
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