PDF(Pubmed)
Abstract：
Cancer is a leading concern and important cause of death worldwide. Cancer is a non-communicable illness defined as uncontrolled division of cells. It can develop into metastatic cancer when tumor cells migrate to other organs. In recent years evidence has emerged that the bioavailability of Asn play a crucial role in cancer metastasis. Asn is a non-essential amino acid formed from an ATP dependent catalyzed reaction by the enzyme asparagine synthetase (ASNS), where Asp and Gln are converted to Asn and Glu, respectively. The human ASNS enzyme consist of 561 amino acids, with a molecular weight of 64 KDa. ASNS governs the activation of transcriptional factors that regulate the process of metastasis. In this work the 3D model of ASNS in E. coli (AS-B) and the human ASNS docked with its different ligands have been used to study the 3D mechanism of the conversion of Asp and Gln to Asn and Glu, in human ASNS. The stability evaluation of the docked complexes was checked by molecular dynamic simulation through the bioinformatic tool Desmond. The binding residues and their interactions can be exploited for the development of inhibitors, as well as for finding new drug molecules against ASNS and prevention of metastatic cancer.
摘要：
癌症是全球范围内的主要关注和重要死亡原因。癌症是一种非传染性疾病，定义为细胞不受控制的分裂。当肿瘤细胞迁移到其他器官时，它可以发展成转移性癌症。近年来，有证据表明Asn的生物利用度在癌症转移中起着至关重要的作用。Asn是由天冬酰胺合成酶（ASNS）的ATP依赖性催化反应形成的非必需氨基酸，其中Asp和Gln转化为Asn和Glu，分别。人ASNS酶由561个氨基酸组成，分子量为64KDa。ASNS控制调节转移过程的转录因子的激活。在这项工作中，ASNS在大肠杆菌（AS-B）中的3D模型和与其不同配体对接的人类ASNS已用于研究Asp和Gln转化为Asn和Glu的3D机制。在人类ASNS中。通过生物信息学工具Desmond通过分子动力学模拟检查对接复合物的稳定性评估。结合残基及其相互作用可用于开发抑制剂，以及寻找新的抗ASNS药物分子和预防转移性癌症。
