Journal of Receptors and Signal Transduction ( IF 2.8 ) Pub Date : 2020-10-18 , DOI: 10.1080/10799893.2020.1835960 Esam S Al-Malki 1
Abstract
The dreadful disease malaria is one among the infectious diseases that comes in third number after the tuberculosis and HIV. This disease is spread by female Anopheles mosquito and caused by the malarial parasite sp notably Plasmodium falciparum. In this, the organism has several enzymes for processing the infection and growth mechanism and among that, the adenylosuccinate lyase is an enzyme that plays a critical role in metabolism and cellular replication via its action in the de novo purine biosynthetic pathway. Adenylosuccinate has been studied for two reaction mechanisms, and in that, the adenylosuccinate to AMP and fumarate is core important. As of now, there have been several studies indicating the reaction mechanism of adenylosuccinate lyase, this study projects the conformations of the reactant and product changes through molecular docking and molecular dynamic simulations. Adenylosuccinate bound complex involves His role in the product than the reactant complex, and the complex shows high flexibility due to fumarate. Thus, identifying the core inhibitor that binds to His rings could be a standard adenylosuccinate lyase inhibitor, that can block the malarial diseases in humans. In addition to the competitive inhibition site, we also predicted the uncompetitive ligand binding site, which suggest the alternate region to be targeted. Thus, from this work, we suggest both competitive and uncompetitive binding regions for the purpose identifying the malarial inhibitors.
中文翻译:
了解疟原虫恶性疟原虫腺苷酸琥珀酸裂解酶受体酶构象的结构见解
摘要
可怕的疾病疟疾是继肺结核和艾滋病毒之后排在第三位的传染病之一。这种疾病由雌性按蚊传播,由疟原虫特别是恶性疟原虫引起。在这种情况下,有机体具有几种用于处理感染和生长机制的酶,其中,腺苷酸琥珀酸裂解酶是一种在代谢和细胞复制中起关键作用的酶。它在从头嘌呤生物合成途径中的作用。腺苷酸琥珀酸已针对两种反应机制进行了研究,其中腺苷酸琥珀酸转化为 AMP 和富马酸是重要的核心。到目前为止,已有多项研究表明腺苷酸琥珀酸裂解酶的反应机理,本研究通过分子对接和分子动力学模拟预测反应物的构象和产物的变化。腺苷酸琥珀酸结合络合物比反应物络合物涉及His作用的产物,而该络合物因富马酸盐而表现出高弹性。因此,确定与 His 环结合的核心抑制剂可能是标准的腺苷酸琥珀酸裂解酶抑制剂,它可以阻断人类的疟疾疾病。除了竞争性抑制位点,我们还预测了非竞争性配体结合位点,这表明要针对的备用区域。因此,从这项工作中,我们建议竞争性和非竞争性结合区域用于鉴定疟疾抑制剂。