Glutamate racemase from Mycobacterium tuberculosis inhibits DNA gyrase by affecting its DNA-binding.
Glutamate racemase (MurI) catalyses the conversion of l-glutamate to d-glutamate, an important component of the bacterial cell wall. MurI from Escherichia coli inhibits DNA gyrase in presence of the peptidoglycan precursor. Amongst the two-glutamate racemases found in Bacillus subtilis, only one inhibits gyrase, in absence of the precursor. Mycobacterium tuberculosis has a single gene encoding glutamate racemase. Action of M.tuberculosis MurI on DNA gyrase activity has been examined and its mode of action elucidated. We demonstrate that mycobacterial MurI inhibits DNA gyrase activity, in addition to its precursor independent racemization function. The inhibition is not species-specific as E.coli gyrase is also inhibited but is enzyme-specific as topoisomerase I activity remains unaltered. The mechanism of inhibition is different from other well-known gyrase inhibitors. MurI binds to GyrA subunit of the enzyme leading to a decrease in DNA-binding of the holoenzyme. The sequestration of the gyrase by MurI results in inhibition of all reactions catalysed by DNA gyrase. MurI is thus not a typical potent inhibitor of DNA gyrase and instead its role could be in modulation of the gyrase activity.
Sengupta
Sugopa
S
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, Karnataka, India.
Shah
Meera
M
Nagaraja
Valakunja
V
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000591:Amino Acid Isomerases / Q000302:isolation & purification / Q000378:metabolism*; D001426:Bacterial Proteins / Q000302:isolation & purification / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D027081:DNA Gyrase / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology*
D001426:Bacterial Proteins; D004247:DNA; D000251:Adenosine Triphosphatases; D000591:Amino Acid Isomerases; C062292:glutamate racemase; D004264:DNA Topoisomerases, Type I; D027081:DNA Gyrase