Undecaprenol kinase: Function, mechanism and substrate specificity of a potential antibiotic target

Brad R. Baker, Callum M. Ives, Ashley Bray, Martin Caffrey, Stephen A. Cochrane

Research output: Contribution to journalReview articlepeer-review

Abstract

The bifunctional undecaprenol kinase/phosphatase (UdpK) is a small, prokaryotic, integral membrane kinase, homologous with Escherichia coli diacylglycerol kinase and expressed by the dgkA gene. In Gram-positive bacteria, UdpK is involved in the homeostasis of the bacterial undecaprenoid pool, where it converts undecaprenol to undecaprenyl phosphate (C55P) and also catalyses the reverse process. C55P is the universal lipid carrier and critical to numerous glycopolymer and glycoprotein biosynthetic pathways in bacteria. DgkA gene expression has been linked to facilitating bacterial growth and survival in response to environmental stressors, as well being implicated as a resistance mechanism to the topical antibiotic bacitracin, by providing an additional route to C55P. Therefore, identification of UdpK inhibitors could lead to novel antibiotic treatments. A combination of homology modelling and mutagenesis experiments on UdpK have been used to identify residues that may be involved in kinase/phosphatase activity. In this review, we will summarise recent work on the mechanism and substrate specificity of UdpK.

Original languageEnglish
Article number113062
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Volume210
Early online date2 Dec 2020
DOIs
Publication statusPublished - 15 Jan 2021

Keywords

  • Antimicrobial resistance
  • Antimicrobial target
  • Kinase
  • Undecaprenol

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