丙二胺酶E2 Ser- cisser - lys催化三联体中Ser/Cys交换影响的分子动力学模拟研究

IF 1.1 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
A. Roy, J. Gauld
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引用次数: 0

摘要

丙二酸酯酶E2催化丙二酸酯(MLA)水解成丙二酸酯和氨。它的活性位点包含一个罕见的ser - cisser - lys3催化基团,这对它的功能至关重要。这个三联体中残基的突变不仅可以提供对其关键特征的洞察,而且还可以潜在地确定它是如何被影响或适应的,即减少或增加。本研究考察了单、双Ser/Cys交换对野生型Ser155-cisSer131-Lys62催化三联体(即Cys155-cisSer131-Lys62 (S155C)、Ser155-cisCys131-Lys62 (S131C)和Cys155-cisCys131-Lys62 (S131C/S155C))的影响。特别是,所得到的取代三元组的动力学和稳定性,以及它们的三元组间残基氢键相互作用,以及与其他邻近残基和MLA底物的相互作用。目前的结果表明,一些突变比其他突变更有影响力。事实上,cisSer131突变为cisys131会破坏三联体,并导致三联体残基(即Ser155、Cys131和Lys62)之间不一致的氢键相互作用。相比之下,在双突变体Cys155-cisCys131-Lys62中,三联体的残基似乎表现出更大的构象稳定性和更一致的氢键相互作用,尽管不一定像野生型那样。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A molecular dynamics simulations investigation on the effects of Ser/Cys exchange in the Ser-cisSer-Lys catalytic triad of Malonamidase E2
The enzyme malonamidase E2 catalytically hydrolyses malonamate (MLA) into malonate and ammonia. Its active site contains an uncommon Ser-cisSer-Lys catalytic triad that is critical to its functioning. Mutations of the residues in this triad can not only provide insight into its key features but can also potentially identify how it may be influenced or adapted, i.e., decreased or increased. In this study, the effects of single and double Ser/Cys exchanges on the wildtype Ser155-cisSer131-Lys62 catalytic triad (i.e., Cys155-cisSer131-Lys62 (S155C), Ser155-cisCys131-Lys62 (S131C), and Cys155-cisCys131-Lys62 (S131C/S155C)) were examined. In particular, the dynamics and stability of the resulting substituted triads was examined along with their inter-triad residue hydrogen bonding interactions as well as those with other nearby residues and the MLA substrate. The present results suggest that some mutations are more impactful than others. Indeed, mutation of cisSer131 to cisCys131 disrupts the triad and causes inconsistent hydrogen bonding interactions among the triad residues (i.e., Ser155, Cys131, and Lys62). In contrast, in the double mutant Cys155-cisCys131-Lys62, the triad’s residues appear to exhibit greater conformation stability with more consistent hydrogen bond interactions, though not necessarily as in the wildtype.
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来源期刊
Canadian Journal of Chemistry
Canadian Journal of Chemistry 化学-化学综合
CiteScore
1.90
自引率
9.10%
发文量
99
审稿时长
1 months
期刊介绍: Published since 1929, the Canadian Journal of Chemistry reports current research findings in all branches of chemistry. It includes the traditional areas of analytical, inorganic, organic, and physical-theoretical chemistry and newer interdisciplinary areas such as materials science, spectroscopy, chemical physics, and biological, medicinal and environmental chemistry. Articles describing original research are welcomed.
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