PDF(Sci-hub)
Abstract：
The pro/N-degron pathway is an evolved protein degradation pathway through the ubiquitin-proteasome system. It is a vital pathway to attain protein homeostasis inside the liver cells with varying glucose levels. N-terminal proline exists in more than 300 proteins in Saccharomyces cerevisiae, but only three of them are the gluconeogenic enzymes; isocitrate lyase (Icl1), fructose-1,6-bisphosphatase (Fbp1), and malate dehydrogenase (Mdh2). The present in silico study aims to structurally illustrate the binding of Icl1 enzyme to Gid4 ligase concerning its peers; Fbp1 and Mdh2. Based on the molecular docking scores and interactions, one can attribute the binding stability of Gid4 with degrons, to peptides of length six up to eight from the N-terminal. Moreover, the percent change in the docking score provides a rationale for the unique Gid4-Icl11-4 interaction. The present study provides insights on the binding attitude of Gid4 ligase to degrons of different lengths, so one will consider in designing peptidomimetics to target Gid4 ligase.
摘要：
pro/N-degron途径是通过泛素-蛋白酶体系统进化的蛋白质降解途径。这是一个至关重要的途径，以获得蛋白质内稳态的肝细胞与不同的葡萄糖水平。N-末端脯氨酸存在于酿酒酵母300多种蛋白质中,但其中只有三种是糖异生酶；异柠檬酸裂解酶（Icl1），果糖-1,6-双磷酸酶（Fbp1），和苹果酸脱氢酶(Mdh2)。目前的计算机研究旨在从结构上说明Icl1酶与Gid4连接酶的结合。Fbp1和Mdh2。根据分子对接得分和相互作用，可以用degrons归因于Gid4的绑定稳定性，从N末端到长度为6到8的肽。此外，对接分数的百分比变化为独特的Gid4-Icl11-4相互作用提供了理论基础.本研究为Gid4连接酶对不同长度的蛋白质的结合态度提供了见解，因此，在设计针对Gid4连接酶的肽模拟物时将考虑。
