Universidade Federal de Rondônia, Porto Velho, RO, Brazil.
J Mol Model. 2010 Mar;16(3):543-50. doi: 10.1007/s00894-009-0557-3. Epub 2009 Aug 11.
Purine nucleoside phosphorylase (PNP) (EC.2.4.2.1) is an enzyme that catalyzes the cleavage of N-ribosidic bonds of the purine ribonucleosides and 2-deoxyribonucleosides in the presence of inorganic orthophosphate as a second substrate. This enzyme is involved in purine-salvage pathway and has been proposed as a promising target for design and development of antimalarial and antibacterial drugs. Recent elucidation of the three-dimensional structure of PNP by X-ray protein crystallography left open the possibility of structure-based virtual screening initiatives in combination with molecular dynamics simulations focused on identification of potential new antimalarial drugs. Most of the previously published molecular dynamics simulations of PNP were carried out on human PNP, a trimeric PNP. The present article describes for the first time molecular dynamics simulations of hexameric PNP from Plasmodium falciparum (PfPNP). Two systems were simulated in the present work, PfPNP in ligand free form, and in complex with immucillin and sulfate. Based on the dynamical behavior of both systems the main results related to structural stability and protein-drug interactions are discussed.
嘌呤核苷磷酸化酶（PNP）（EC.2.4.2.1）是一种酶，它在无机正磷酸盐作为第二底物的存在下催化嘌呤核糖核苷和脱氧核糖核苷的 N-糖苷键的断裂。该酶参与嘌呤补救途径，并已被提议作为设计和开发抗疟和抗菌药物的有前途的靶标。最近通过 X 射线蛋白晶体学阐明 PNP 的三维结构，为结合分子动力学模拟的基于结构的虚拟筛选计划开辟了可能性，这些计划侧重于鉴定潜在的新抗疟药物。以前发表的大多数 PNP 的分子动力学模拟都是在人 PNP（三聚体 PNP）上进行的。本文首次描述了来自恶性疟原虫（PfPNP）的六聚体 PNP 的分子动力学模拟。在本工作中模拟了两个系统，无配体形式的 PfPNP 和与 immucillin 和硫酸盐形成复合物的 PfPNP。基于两个系统的动力学行为，讨论了与结构稳定性和蛋白-药物相互作用相关的主要结果。
