Structure and function of cytidine monophosphate kinase from Yersinia pseudotuberculosis, essential for virulence but not for survival

N. J. Walker, E. A. Clark, D. C. Ford, H. L. Bullifent, E. V. Mcalister, M. L. Duffield, K. R. Acharya, P. C. F. Oyston

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The need for new antibiotics has become pressing in light of the emergence of antibiotic-resistant strains of human pathogens. Yersinia pestis, the causative agent of plague, is a public health threat and also an agent of concern in biodefence. It is a recently emerged clonal derivative of the enteric pathogen Yersinia pseudotuberculosis. Previously, we developed a bioinformatic approach to identify proteins that may be suitable targets for antimicrobial therapy and in particular for the treatment of plague. One such target was cytidine monophosphate (CMP) kinase, which is an essential gene in some organisms. Previously, we had thought CMP kinase was essential for Y. pseudotuberculosis, but by modification of the mutagenesis approach, we report here the production and characterization of a Δcmk mutant. The isogenic mutant had a growth defect relative to the parental strain, and was highly attenuated in mice. We have also elucidated the structure of the CMP kinase to 2.32 Å, and identified three key residues in the active site that are essential for activity of the enzyme. These findings will have implications for the development of novel CMP kinase inhibitors for therapeutic use.
Original languageEnglish
Article number120142
JournalOpen Biology
Volume2
Issue numberDec
DOIs
Publication statusPublished - 5 Dec 2012

Fingerprint Dive into the research topics of 'Structure and function of cytidine monophosphate kinase from Yersinia pseudotuberculosis, essential for virulence but not for survival'. Together they form a unique fingerprint.

  • Projects

    Cite this

    Walker, N. J., Clark, E. A., Ford, D. C., Bullifent, H. L., Mcalister, E. V., Duffield, M. L., Acharya, K. R., & Oyston, P. C. F. (2012). Structure and function of cytidine monophosphate kinase from Yersinia pseudotuberculosis, essential for virulence but not for survival. Open Biology, 2(Dec), [120142]. https://doi.org/10.1098/rsob.120142