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Crystal structure of Escherichia coli purine nucleoside phosphorylase complexed with acyclovir
Author(s) -
Timofeev Vladimir I.,
Zhukhlistova Nadezhda E.,
Abramchik Yuliya A.,
Muravieva Tatiana I.,
Esipov Roman S.,
Kuranova Inna P.
Publication year - 2018
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 37
ISSN - 2053-230X
DOI - 10.1107/s2053230x18008087
Subject(s) - phosphorolysis , purine nucleoside phosphorylase , guanosine , purine , chemistry , escherichia coli , stereochemistry , nucleotide salvage , nucleoside , thymidine phosphorylase , biochemistry , enzyme , nucleotide , gene
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.