Mycobacterial Ser/Thr protein kinases and phosphatases: physiological roles and therapeutic potential.
Reversible protein phosphorylation is a major regulation mechanism of fundamental biological processes, not only in eukaryotes but also in bacteria. A growing body of evidence suggests that Ser/Thr phosphorylation play important roles in the physiology and virulence of Mycobacterium tuberculosis, the etiological agent of tuberculosis. This pathogen uses 'eukaryotic-like' Ser/Thr protein kinases and phosphatases not only to regulate many intracellular metabolic processes, but also to interfere with signaling pathways of the infected host cell. Disrupting such processes by means of selective inhibitors may thus provide new pharmaceutical weapons to combat the disease. Here we review the current knowledge on Ser/Thr protein kinases and phosphatases in M. tuberculosis, their regulation mechanisms and putative substrates, and we explore their therapeutic potential as possible targets for the development of new anti-mycobacterial compounds.
Wehenkel
Annemarie
A
Unité de Biochimie Structurale, URA 2185 CNRS, Institut Pasteur, 25 rue du Docteur Roux, F-75724, Paris Cedex 15, France.
Bellinzoni
Marco
M
Graña
Martin
M
Duran
Rosario
R
Villarino
Andrea
A
Fernandez
Pablo
P
Andre-Leroux
Gwénaëlle
G
England
Patrick
P
Takiff
Howard
H
Cerveñansky
Carlos
C
Cole
Stewart T
ST
Alzari
Pedro M
PM
D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014376:Tuberculosis / Q000188:drug therapy; D014774:Virulence
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases