Screening serine/threonine and tyrosine kinase inhibitors for histidine kinase inhibition

Kaelyn E. Wilke, Conrad A. Fihn, Erin E. Carlson

Research output: Contribution to journalArticle

3 Scopus citations


Histidine kinases of bacterial two-component systems are promising antibacterial targets. Despite their varied, numerous roles, enzymes in the histidine kinase superfamily share a catalytic core that may be exploited to inhibit multiple histidine kinases simultaneously. Characterized by the Bergerat fold, the features of the histidine kinase ATP-binding domain are not found in serine/threonine and tyrosine kinases. However, because each kinase family binds the same ATP substrate, we sought to determine if published serine/threonine and tyrosine kinase inhibitors contained scaffolds that would also inhibit histidine kinases. Using select assays, 222 inhibitors from the Roche Published Kinase Set were screened for binding, deactivation, and aggregation of histidine kinases. Not only do the results of our screen support the distinctions between ATP-binding domains of different kinase families, but the lead molecule identified also presents inspiration for further histidine kinase inhibitor development.

Original languageEnglish (US)
Pages (from-to)5322-5326
Number of pages5
JournalBioorganic and Medicinal Chemistry
StatePublished - Oct 15 2018


  • Antibacterial targets
  • Histidine kinases
  • Inhibitors
  • Roche Published Kinase Set
  • Two-component systems

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