Escherichia coli purine nucleoside phosphorylase (PNP)

Escherichia coli purine nucleoside phosphorylase (PNP) is a hexameric enzyme belonging to the family I nucleoside phosphorylases (EC 2.4.2.1) which catalyzes the reversible phosphorolysis of purine ribonucleosides and 2'-deoxyribonucleosides, generating free purine bases and ribose 1-phosphate. It plays a key role in the purine salvage pathway, enabling E. coli to efficiently recycle nucleosides for DNA and RNA synthesis. E. coli PNP is distinguished from the mammalian (trimeric) and other bacterial PNPs by broader substrate specificity and hexameric quaternary structure. Due to differences in substrate preference and structure compared to human PNP, E. coli PNP is the focus of drug design and gene therapy approaches, especially where selective activation of cytotoxic prodrugs is desired. The enzyme has been crystallized in complex with drugs such as acyclovir, illuminating details important for rational drug design.

Other names

PNPPurine-nucleoside phosphorylase DeoD-typeEC 2.4.2.1XapA gene product (for PNP-II)

Phosphorolysis: cleavage of N-glycosidic bonds using orthophosphate, generating ribose-1-phosphate and free purine base Prodrug activation: conversion of an inactive substrate to an active cytotoxic compound in cells expressing E. coli PNP (used in cancer gene therapy)