Bacterial Protein-Tyrosine Kinases

Abstract

Bacteria and Eukarya share essentially the same family ofprotein-serine/threonine kinases, also known as the Hanks-type kinases.However, when it comes to protein-tyrosine phosphorylation, bacteriaseem to have gone their own way. Bacterial protein-tyrosine kinases(BY-kinases) are bacterial enzymes that are unique in exploiting theATP/GTP-binding Walker motif to catalyze phosphorylation of proteintyrosine residues. Characterized for the first time only a decade ago,BY-kinases have now come to the fore. Important regulatory roles havebeen linked with these enzymes, via their involvement inexopolysaccharide production, virulence, DNA metabolism, stress responseand other key functions of the bacterial cell. BY-kinases act throughautophosphorylation (mainly in exopolysaccharide production) andphosphorylation of other proteins, which have in most cases been shownto be activated by tyrosine phosphorylation. Protein-tyrosinephosphorylation in bacteria is particular with respect to very lowoccupancy of phosphorylation sites in vivo; this has represented a majorchallenge for detection techniques. Only the recent breakthroughs ingel-free high resolution mass spectrometry allowed the systematicdetection of phosphorylated tyrosines by phosphoprotomics studies inbacteria. Other pioneering studies conducted in recent years, such asthe first structures of BY-kinases and biochemical and phyiologicalstudies of new BY-kinase substrates significantly furthered ourunderstanding of these enzymes and highlighted their importance inbacterial physiology. Having no orthologues in Eukarya, BY-kinases arereceiving a growing attention from the biomedical field, since theyrepresent a particularly promising target for anti-bacterial drugdesign.