Inhibition of DNA gyrase activity by Mycobacterium smegmatis MurI.
Glutamate racemase (MurI) catalyzes the interconversion of l-glutamate to d-glutamate, one of the essential amino acids present in the peptidoglycan. In addition to this essential enzymatic function, MurI from Escherichia coli, Bacillus subtilis and Mycobacterium tuberculosis inhibit DNA gyrase activity. A single gene for murI found in the Mycobacterium smegmatis genome was cloned and overexpressed in a homologous expression system to obtain a highly soluble enzyme. In addition to the racemization activity, M. smegmatis MurI inhibits DNA gyrase activity by preventing DNA binding of gyrase. The sequestration of the gyrase by MurI results in inhibition of all reactions catalyzed by DNA gyrase. More importantly, MurI overexpression in vivo in mycobacterial cells provides protection against the action of ciprofloxacin. The DNA gyrase-inhibitory property thus appears to be a typical characteristic of MurI and would have probably evolved to either modulate the function of the essential housekeeping enzyme or to provide protection to gyrase against gyrase inhibitors, which cause double-strand breaks in the genome.
Sengupta
Sugopa
S
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
Nagaraja
Valakunja
V
D000591:Amino Acid Isomerases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002939:Ciprofloxacin / Q000494:pharmacology; D003001:Cloning, Molecular; D024881:Drug Resistance, Bacterial / Q000235:genetics; D018628:Gene Dosage; D018698:Glutamic Acid / Q000378:metabolism; D020102:Mycobacterium smegmatis / Q000201:enzymology* / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D059005:Topoisomerase II Inhibitors
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D059005:Topoisomerase II Inhibitors; D018698:Glutamic Acid; D002939:Ciprofloxacin; D000591:Amino Acid Isomerases; C062292:glutamate racemase