论文部分内容阅读
酰基辅酶硫酯酶(Acyl-CoA thioesterases,ACOTs),也被称作酰基辅酶A水解酶,是一类能够水解酰基辅酶A酯类水解的酶,在脂肪酸的代谢中起着重要的作用。文中通过将序列分析得到的ACOT1的有害突变序列(ACOT1_MULT)和野生型序列利用同源建模的方法得到了相应的蛋白结构,并利用分子动力学模拟的方法研究了突变氨基酸对蛋白结构造成的影响。研究结果发现:突变蛋白在分子动力学过程中活性中心上面的“盖子”(LEU374-SER380)区域打开,而野生型一直处于关闭状态。通过对氢键和疏水作用的分析发现,突变位置的氨基酸(ALA189THR)与蛋白序列中的GLY169形成了新的氢键,突变残基附近的氢键也发生了很大的变化,导致了邮水解酶区域的第3个β折叠的末端Loop区(160Loop)朝着外侧的亲水性区域拉伸。160Loop区域的变化使得它与“盖子”区域之间的疏水相互作用消失,“盖子”区域的稳定性下降,并最终导致了“盖子”的打开。该结果对ACOT1蛋白相关的人类免疫病毒缺陷疾病和附睾炎等疾病的发病机理的研究具有很好的借鉴作用,同时也为基于该活性区域的抑制剂筛选工作提供了新的靶点。
Acyl-CoA thioesterases (ACOTs), also known as acyl-CoA hydrolases, are a class of enzymes that hydrolyze acyl-CoA esters and play an important role in the metabolism of fatty acids. In this paper, the corresponding protein structure was obtained by homology modeling of the ACOT1 deleterious mutation sequence (ACOT1_MULT) and the wild-type sequence obtained by sequence analysis, and the effect of the mutant amino acid on the protein structure was also studied by means of molecular dynamics simulation influences. The results showed that the mutein was opened in the “lid” (LEU374-SER380) region above the active center in the molecular dynamics process, while the wild type remained closed. Through the analysis of hydrogen bond and hydrophobic interaction, we find that the amino acid at the mutation site (ALA189THR) forms a new hydrogen bond with GLY169 in the protein sequence, and the hydrogen bond near the mutant residue also changes greatly, The third Beta-folded terminal Loop region (160Loop) of the enzyme region is stretched toward the outer hydrophilic region. The 160Loop area changes so that the hydrophobic interaction between it and the “lid” area disappears, the stability of the “lid” area drops, and eventually the “lid” opens. The results of the ACOT1 protein-related human immunodeficiency virus disease and epididymitis and other diseases pathogenesis study has a good reference, but also based on the active region of the inhibitor screening work provides a new target.