Timofeev Vladimir I, Zhukhlistova Nadezhda E, Abramchik Yuliya A, Muravieva Tatiana I, Esipov Roman S, Kuranova Inna P
Shubnikov Institute of Crystallography, Federal Scientific Research Centre `Crystallography and Photonics' of Russian Academy of Sciences, Leninsky Prospekt 59, Moscow 119333, Russian Federation.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street 16/10, Moscow 117997, Russian Federation.
Acta Crystallogr F Struct Biol Commun. 2018 Jul 1;74(Pt 7):402-409. doi: 10.1107/S2053230X18008087. Epub 2018 Jun 26.
Escherichia coli purine nucleoside phosphorylase (PNP), which catalyzes the reversible phosphorolysis of purine ribonucleosides, belongs to the family I hexameric PNPs. Owing to their key role in the purine salvage pathway, PNPs are attractive targets for drug design against some pathogens. Acyclovir (ACV) is an acyclic derivative of the PNP substrate guanosine and is used as an antiviral drug for the treatment of some human viral infections. The crystalline complex of E. coli PNP with acyclovir was prepared by co-crystallization in microgravity using counter-diffusion through a gel layer in a capillary. The structure of the E. coli PNP-ACV complex was solved at 2.32 Å resolution using the molecular-replacement method. The ACV molecule is observed in two conformations and sulfate ions were located in both the nucleoside-binding and phosphate-binding pockets of the enzyme. A comparison with the complexes of other hexameric and trimeric PNPs with ACV shows the similarity in acyclovir binding by these enzymes.
大肠杆菌嘌呤核苷磷酸化酶（PNP）催化嘌呤核糖核苷的可逆磷酸解，属于I型六聚体PNP家族。由于PNP在嘌呤补救途径中起关键作用，因此它们是针对某些病原体进行药物设计的有吸引力的靶点。阿昔洛韦（ACV）是PNP底物鸟苷的无环衍生物，用作治疗某些人类病毒感染的抗病毒药物。通过在微重力条件下通过毛细管中的凝胶层进行反向扩散共结晶，制备了大肠杆菌PNP与阿昔洛韦的晶体复合物。使用分子置换法以2.32Å的分辨率解析了大肠杆菌PNP-ACV复合物的结构。观察到ACV分子有两种构象，并且硫酸根离子位于酶的核苷结合口袋和磷酸结合口袋中。与其他六聚体和三聚体PNP与ACV的复合物进行比较，显示这些酶在阿昔洛韦结合方面具有相似性。
