Analysis of the NH2-terminal 87th amino acid of Escherichia coli GyrA in quinolone-resistance.
The functional contributions of amino acid residue Asp87 of Escherichia coli gyrase A protein (GyrA) was analyzed by site-directed mutagenesis. We generated a series of mutants, in which Asp87 of GyrA was changed to Ala, Val, Phe, Asn, Ser, and Lys. By genetic analysis of gyrA genes in a gyrA temperature-sensitive (Ts) background, it was shown that all these mutations caused the quinolone-resistance. These results indicate that the 87th amino acid of E. coli GyrA must have negative charge in expressing the phenotype of quinolone sensitivity. These findings also suggest that the carboxyl group of Asp87 may interact with quinolone drugs.
Yonezawa
M
M
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Takahata
M
M
Banzawa
N
N
Matsubara
N
N
Watanabe
Y
Y
Narita
H
H
D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001224:Aspartic Acid; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000187:drug effects / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects / Q000235:genetics*; D005798:Genes, Bacterial / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D013329:Structure-Activity Relationship
D042462:4-Quinolones; D000890:Anti-Infective Agents; D017931:DNA Primers; D001224:Aspartic Acid; D004250:DNA Topoisomerases, Type II