Metabolic functions of microbial nucleoside diphosphate kinases

This article summarizes research from our laboratory on two aspects of the biochemistry of nucleoside diphosphate kinase from Escherichia coli-first, its interactions with several T4 bacteriophage-coded enzymes, as part of a multienzyme complex for deoxyribonucleoside triphosphate biosynthesis. We i dentify some of the specific interactions and discuss whether the complex i s linked physically or functionally with the T4 DNA replication machinery, or replisome. Second, we discuss phenotypes of an E. coli mutant strain car rying a targeted deletion of ndk, the structural gene for nucleoside diphos phate kinase. How do bacteria lacking this essential housekeeping enzyme sy nthesize nucleoside triphosphates? In view of the specific interactions of nucleoside diphosphate kinase with T4 enzymes of DNA metabolism, how does T 4 multiply after infection of this host? Finally, the ndk disruption strain has highly biased nucleoside triphosphate pools, including elevations of t he CTP and dCTP pools of 7- and 23-fold, respectively. Accompanied by these biased nucleotide pools is a strong mutator phenotype. What is the biochem ical basis for the pool abnormalities and what are the mutagenic mechanisms ? We conclude with brief references to related work in other laboratories.