Bacterial tyrosine-kinases: structure-function analysis and therapeutic potential.
Since the characterization of genes encoding Ser/Thr-kinases and Tyr-kinases in bacteria, in 1991 and 1997, respectively, a growing body of evidence has been reported showing the important role of these enzymes in the regulation of bacterial physiology. While most Ser/Thr-kinases share structural similarity with their eukaryotic counterparts, it seems that bacteria have developed their own Tyr-kinases to catalyze protein phosphorylation on tyrosine. Different types of Tyr-kinases have been identified in bacteria and a large number of them are similar to ATP-binding proteins with Walker motifs. These enzymes have been grouped in the same family (BY-kinases) and the crystal structures of two of them have been recently characterized. Phosphoproteome analysis suggest that BY-kinases are involved in several cellular processes and to date, the best-characterized role of BY-kinases concerns the control of extracellular polysaccharide synthesis. Knowing the role of these compounds in the virulence of bacterial pathogens, BY-kinases can be considered as promising targets to combat some diseases. Here, we review the current knowledge on BY-kinases and discuss their potential for the development of new antibiotics.
Grangeasse
Christophe
C
Institut de Biologie et Chimie des Protéines, UMR 5086, CNRS, Université de Lyon, 7, passage du Vercors, 69367 Lyon cedex 07, France. c.grangeasse@ibcp.fr
Terreux
Raphaël
R
Nessler
Sylvie
S
D020816:Amino Acid Motifs / Q000502:physiology; D001419:Bacteria / Q000201:enzymology*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000201:enzymology*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000627:therapeutic use*; D017434:Protein Structure, Tertiary / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011505:Protein-Tyrosine Kinases