The Macromolecular Machines that Duplicate the Escherichia coli Chromosome as Targets for Drug Discovery

Abstract

DNA replication is an essential process. Although the fundamental strategies to duplicate chromosomes are similar in all free-living organisms, the enzymes of the three domains of life that perform similar functions in DNA replication differ in amino acid sequence and their three-dimensional structures. Moreover, the respective proteins generally utilize different enzymatic mechanisms. Hence, the replication proteins that are highly conserved among bacterial species are attractive targets to develop novel antibiotics as the compounds are unlikely to demonstrate off-target effects. For those proteins that differ among bacteria, compounds that are species-specific may be found. Escherichia coli has been developed as a model system to study DNA replication, serving as a benchmark for comparison. This review summarizes the functions of individual E. coli proteins, and the compounds that inhibit them.

Keywords

• DNA replication
• Escherichia coli
• inhibitors
• replisome
• replication fork
• initiation
• replication origin
• DnaA
• DnaB
• DnaC
• primase
• DnaG
• SSB
• DNA gyrase
• topoisomerase IV
• DNA polymerase I
• DNA polymerase III holoenzyme
• sliding clamp
• clamp loader
• DNA ligase