Mutagenesis in the alpha3alpha4 GyrA helix and in the Toprim domain of GyrB refines the contribution of Mycobacterium tuberculosis DNA gyrase to intrinsic resistance to quinolones.
The replacement of M74 in GyrA, A83 in GyrA, and R447 in GyrB of Mycobacterium tuberculosis gyrase by their Escherichia coli homologs resulted in active enzymes as quinolone susceptible as the E. coli gyrase. This demonstrates that the primary structure of gyrase determines intrinsic quinolone resistance and was supported by a three-dimensional model of N-terminal GyrA.
Matrat
Stéphanie
S
Université Pierre et Marie Curie-Paris 6, EA1541, Paris F-75013, France.
Aubry
Alexandra
A
Mayer
Claudine
C
Jarlier
Vincent
V
Cambau
Emmanuelle
E
D000595:Amino Acid Sequence; D000995:Antitubercular Agents / Q000494:pharmacology; D027081:DNA Gyrase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D017433:Protein Structure, Secondary; D015363:Quinolones / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D000995:Antitubercular Agents; D015363:Quinolones; D027081:DNA Gyrase