Slow polymerization of Mycobacterium tuberculosis FtsZ.
The essential cell division protein, FtsZ, from Mycobacterium tuberculosis has been expressed in Escherichia coli and purified. The recombinant protein has GTPase activity typical of tubulin and other FtsZs. FtsZ polymerization was studied using 90 degrees light scattering. The mycobacterial protein reaches maximum polymerization much more slowly ( approximately 10 min) than E. coli FtsZ. Depolymerization also occurs slowly, taking 1 h or longer under most conditions. Polymerization requires both Mg(2+) and GTP. The minimum concentration of FtsZ needed for polymerization is 3 microM. Electron microscopy shows that polymerized M. tuberculosis FtsZ consists of strands that associate to form ordered aggregates of parallel protofilaments. Ethyl 6-amino-2, 3-dihydro-4-phenyl-1H-pyrido[4,3-b][1,4]diazepin-8-ylcarbamate+ ++ (SRI 7614), an inhibitor of tubulin polymerization synthesized at Southern Research Institute, inhibits M. tuberculosis FtsZ polymerization, inhibits GTP hydrolysis, and reduces the number and sizes of FtsZ polymers.
White
E L
EL
Drug Discovery Division, Southern Research Institute, Birmingham, AL 35205, USA. white@sri.org
Ross
L J
LJ
Reynolds
R C
RC
Seitz
L E
LE
Moore
G D
GD
Borhani
D W
DW
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D003598:Cytoskeletal Proteins; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D008027:Light; D009169:Mycobacterium tuberculosis; D011994:Recombinant Proteins / Q000378:metabolism; D012542:Scattering, Radiation; D020539:Sequence Analysis, Protein; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; D011994:Recombinant Proteins; D006160:Guanosine Triphosphate