Mode of action of GR122222X, a novel inhibitor of bacterial DNA gyrase.
GR122222X is a potent inhibitor of the supercoiling reaction of bacterial DNA gyrase. We show that this compound binds stoichiometrically to inactivate the ATPase activity of a 43-kDa N-terminal fragment of the B subunit and competitively inhibits the binding of a radiolabelled coumarin drug to N-terminal fragments of GyrB. These and other data suggest that GR122222X has a mode of action similar, but not identical, to that of coumarin antibiotics.
Oram
M
M
Department of Cellular and Molecular Sciences, University of London, United Kingdom.
Dosanjh
B
B
Gormley
N A
NA
Smith
C V
CV
Fisher
L M
LM
Maxwell
A
A
Duncan
K
K
D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D009675:Novobiocin / Q000378:metabolism / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors
D010456:Peptides, Cyclic; D059005:Topoisomerase II Inhibitors; C088717:GR 122222X; D009675:Novobiocin; D004250:DNA Topoisomerases, Type II