scholarly journals Novel quinolone resistance mutations of the Escherichia coli DNA gyrase A protein: enzymatic analysis of the mutant proteins.

1991 ◽  
Vol 35 (2) ◽  
pp. 335-340 ◽  
Author(s):  
P Hallett ◽  
A Maxwell
Keyword(s):  
Escherichia Coli ◽  
Dna Gyrase ◽  
Quinolone Resistance ◽  
Enzymatic Analysis ◽  
Resistance Mutations ◽  
Mutant Proteins ◽  
Gyrase A

scholarly journals Mutation in the DNA Gyrase A Gene ofEscherichia coli That Expands the Quinolone Resistance-Determining Region

2001 ◽  
Vol 45 (8) ◽  
pp. 2378-2380 ◽  
Author(s):  
S. Marvin Friedman ◽  
Tao Lu ◽  
Karl Drlica
Keyword(s):  
Escherichia Coli ◽  
Amino Acids ◽  
Amino Acid ◽  
Dna Gyrase ◽  
Ofescherichia Coli ◽  
Quinolone Resistance ◽  
Gyrase A

ABSTRACT In three Escherichia coli mutants, a change (Ala-51 to Val) in the gyrase A protein outside the standard quinolone resistance-determining region (QRDR) lowered the level of quinolone susceptibility more than changes at amino acids 67, 82, 84, and 106 did. Revision of the QRDR to include amino acid 51 is indicated.

scholarly journals Quinolone-Binding Pocket of DNA Gyrase: Role of GyrB

2002 ◽  
Vol 46 (6) ◽  
pp. 1805-1815 ◽  
Author(s):  
Jonathan Heddle ◽  
Anthony Maxwell
Keyword(s):  
Conformational Changes ◽  
Structural Data ◽  
Dna Gyrase ◽  
Binding Pocket ◽  
Quinolone Resistance ◽  
Resistance Mutations ◽  
Mutant Proteins ◽  
Close Proximity ◽  
To Come

ABSTRACT DNA gyrase is a prokaryotic type II topoisomerase and a major target of quinolone antibacterials. The majority of mutations conferring resistance to quinolones arise within the quinolone resistance-determining region of GyrA close to the active site (Tyr122) where DNA is bound and cleaved. However, some quinolone resistance mutations are known to exist in GyrB. Present structural data suggest that these residues lie a considerable distance from the quinolone resistance-determining region, and it is not obvious how they affect quinolone action. We have made and purified two such mutant proteins, GyrB(Asp426→Asn) and GyrB(Lys447→Glu), and characterized them in vitro. We found that the two proteins behave similarly to GyrA quinolone-resistant proteins. We showed that the mutations exert their effect by decreasing the amount of quinolone bound to a gyrase-DNA complex. We suggest that the GyrB residues form part of a quinolone-binding pocket that includes DNA and the quinolone resistance-determining region in GyrA and that large conformational changes during the catalytic cycle of the enzyme allow these regions to come into close proximity.

scholarly journals Interaction between DNA Gyrase and Quinolones: Effects of Alanine Mutations at GyrA Subunit Residues Ser83and Asp87

2001 ◽  
Vol 45 (7) ◽  
pp. 1994-2000 ◽  
Author(s):  
Faye M. Barnard ◽  
Anthony Maxwell
Keyword(s):  
Dna Cleavage ◽  
Double Mutant ◽  
Dna Gyrase ◽  
Dna Supercoiling ◽  
Drug Binding ◽  
Resistance Mutations ◽  
Mutant Proteins ◽  
Gyrase A ◽  
A Subunit ◽  
High Level

ABSTRACT DNA gyrase is a target of quinolone antibacterial agents, but the molecular details of the quinolone-gyrase interaction are not clear. Quinolone resistance mutations frequently occur at residues Ser83 and Asp87 of the gyrase A subunit, suggesting that these residues are involved in drug binding. Single and double alanine substitutions were created at these positions (Ala83, Ala87, and Ala83Ala87), and the mutant proteins were assessed for DNA supercoiling, DNA cleavage, and resistance to a number of quinolone drugs. The Ala83 mutant was fully active in supercoiling, whereas the Ala87 and the double mutant were 2.5- and 4- to 5-fold less active, respectively; this loss in activity may be partly due to an increased affinity of these mutant proteins for DNA. Supercoiling inhibition and cleavage assays revealed that the double mutant has a high level of resistance to certain quinolones while the mutants with single alanine substitutions show low-level resistance. Using a drug-binding assay we demonstrated that the double-mutant enzyme-DNA complex has a lower affinity for ciprofloxacin than the wild-type complex. Based on the pattern of resistance to a series of quinolones, an interaction between the C-8 group of the quinolone and the double-mutant gyrase in the region of residues 83 and 87 is proposed.

scholarly journals Cloning and simplified purification of Escherichia coli DNA gyrase A and B proteins.

1984 ◽  
Vol 259 (14) ◽  
pp. 9199-9201 ◽  
Author(s):  
K Mizuuchi ◽  
M Mizuuchi ◽  
M H O'Dea ◽  
M Gellert
Keyword(s):  
Escherichia Coli ◽  
Dna Gyrase ◽  
Gyrase A

scholarly journals Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli.

1990 ◽  
Vol 34 (6) ◽  
pp. 1271-1272 ◽  
Author(s):  
H Yoshida ◽  
M Bogaki ◽  
M Nakamura ◽  
S Nakamura
Keyword(s):  
Escherichia Coli ◽  
Dna Gyrase ◽  
Quinolone Resistance ◽  
Gyra Gene

scholarly journals A Molecular Docking Study of N-Ferrocenylmethylnitroanilines as Potential Anticancer Drugs

2016 ◽  
Vol 2 ◽  
pp. 5-12 ◽  
Author(s):  
Touhami Lanez ◽  
Elhafnaoui Lanez
Keyword(s):  
Escherichia Coli ◽  
Molecular Docking ◽  
Protein Structure ◽  
Dna Gyrase ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Molegro Virtual Docker ◽  
Gyrase A

In the present study, the interaction of the protein structure of Escherichia coli DNA Gyrase-A (EcGyr-A) extracted from protein data bank (PDB Code: 1AB4) with ligands N-ferrocenylmethyl-2-nitroaniline (2FMNA), N-ferrocenylmethyl-3-nitroaniline (3FMNA) and N-ferrocenylmethyl-4-nitroaniline (4FMNA) were investigated by performing docking studies using the Molegro Virtual Docker (MVD) software. The results obtained showed that the best poses which is derived from MolDock score for Escherichia coli DNA Gyrase-A were respectively equal to-92.0111, -96.0866 and-95.6808 with reranking score equal to-40.9575, -73.4476 and-73.6423. Calculations revealed that 3FMNA react strongly with EcGyr-A followed by 4-FMNA and 2-FMNA.

scholarly journals Mutagenesis in the α3α4 GyrA Helix and in the Toprim Domain of GyrB Refines the Contribution of Mycobacterium tuberculosis DNA Gyrase to Intrinsic Resistance to Quinolones

2008 ◽  
Vol 52 (8) ◽  
pp. 2909-2914 ◽  
Author(s):  
Stéphanie Matrat ◽  
Alexandra Aubry ◽  
Claudine Mayer ◽  
Vincent Jarlier ◽  
Emmanuelle Cambau
Keyword(s):  
Escherichia Coli ◽  
Mycobacterium Tuberculosis ◽  
Primary Structure ◽  
Three Dimensional ◽  
Dna Gyrase ◽  
Quinolone Resistance ◽  
Dimensional Model ◽  
Three Dimensional Model ◽  
Intrinsic Resistance ◽  
E Coli

ABSTRACT 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.

scholarly journals Prevalence of Plasmid-Mediated Quinolone Resistance

2003 ◽  
Vol 47 (2) ◽  
pp. 559-562 ◽  
Author(s):  
George A. Jacoby ◽  
Nancy Chow ◽  
Ken B. Waites
Keyword(s):  
Medical Center ◽  
Dna Gyrase ◽  
The United States ◽  
Quinolone Resistance ◽  
Clinical Strain ◽  
University Of Alabama ◽  
Repeat Family ◽  
Gyrase A ◽  
The University ◽  
Microcin B17

ABSTRACT Quinolone resistance encoded by the qnr gene and mediated by plasmid pMG252 was discovered in a clinical strain of Klebsiella pneumoniae that was isolated in 1994 at the University of Alabama at Birmingham Medical Center. The gene codes for a protein that protects DNA gyrase from quinolone inhibition and that belongs to the pentapeptide repeat family of proteins. The prevalence of the gene has been investigated by using PCR with qnr-specific primers with a sample of more than 350 gram-negative strains that originated in 18 countries and 24 states in the United States and that included many strains with plasmid-mediated AmpC or extended spectrum β-lactamase enzymes. qnr was found in isolates from the University of Alabama at Birmingham only during 6 months in 1994, despite the persistence of the gene for FOX-5 β-lactamase, which is linked to qnr on pMG252. Isolates from other locations were negative for qnr. The prevalence of mcbG in the same sample was also examined. mcbG encodes another member of the pentapeptide repeat family and is involved in immunity to microcin B17, which, like quinolones, targets DNA gyrase. A single clinical isolate contained mcbG on a transmissible R plasmid. This plasmid and one carrying the complete microcin B17 operon slightly decreased sparfloxacin susceptibility but had a much less protective effect than pMG252. Plasmid-mediated quinolone resistance was thus rare in the sample examined.

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