scholarly journals Mapping Simocyclinone D8 Interaction with DNA Gyrase: Evidence for a New Binding Site on GyrB

2009 ◽  
Vol 54 (1) ◽  
pp. 213-220 ◽  
Author(s):  
C. Sissi ◽  
E. Vazquez ◽  
A. Chemello ◽  
L. A. Mitchenall ◽  
A. Maxwell ◽  
...  
Keyword(s):  
Dna Gyrase ◽  
Coumarin Derivative ◽  
Streptomyces Antibioticus ◽  
B Subunit ◽  
Terminal Domain ◽  
Antiproliferative Agent ◽  
Gyrase A ◽  
A Subunit ◽  
The Individual ◽  
Simocyclinone D8

ABSTRACT Simocyclinone D8, a coumarin derivative isolated from Streptomyces antibioticus Tü 6040, represents an interesting new antiproliferative agent. It was originally suggested that this drug recognizes the GyrA subunit and interferes with the gyrase catalytic cycle by preventing its binding to DNA. To further characterize the mode of action of this antibiotic, we investigated its binding to the reconstituted DNA gyrase (A2B2) as well as to its GyrA and GyrB subunits and the individual domains of these proteins, by performing protein melting and proteolytic digestion studies as well as inhibition assays. Two binding sites were identified, one (anticipated) in the N-terminal domain of GyrA (GyrA59) and the other (unexpected) at the C-terminal domain of GyrB (GyrB47). Stabilization of the A subunit appears to be considerably more effective than stabilization of the B subunit. Our data suggest that these two distinct sites could cooperate in the reconstituted enzyme.

scholarly journals The pivot point arginines identified in the β-pinwheel structure of C-terminal domain from Salmonella Typhi DNA Gyrase A subunit

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ekta Sachdeva ◽  
Gurpreet Kaur ◽  
Pragya Tiwari ◽  
Deepali Gupta ◽  
Tej P. Singh ◽  
...  
Keyword(s):  
Dna Gyrase ◽  
Salmonella Typhi ◽  
Pivot Point ◽  
Terminal Domain ◽  
Gyrase A ◽  
A Subunit

scholarly journals The key DNA-binding residues in the C-terminal domain of Mycobacterium tuberculosis DNA gyrase A subunit (GyrA)

2006 ◽  
Vol 34 (19) ◽  
pp. 5650-5659 ◽  
Author(s):  
You-Yi Huang ◽  
Jiao-Yu Deng ◽  
Jing Gu ◽  
Zhi-Ping Zhang ◽  
Anthony Maxwell ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dna Binding ◽  
Dna Gyrase ◽  
Terminal Domain ◽  
Gyrase A ◽  
A Subunit ◽  
Binding Residues

Changed properties of the A subunit in DNA gyrase with a B subunit mutation

1982 ◽  
Vol 186 (4) ◽  
pp. 572-574 ◽  
Author(s):  
E. S. Bogdanova ◽  
S. M. Mirkin ◽  
Zh. G. Shmerling
Keyword(s):  
Dna Gyrase ◽  
B Subunit ◽  
A Subunit

scholarly journals The C-terminal domain of DNA gyrase A adopts a DNA-bending  -pinwheel fold

2004 ◽  
Vol 101 (19) ◽  
pp. 7293-7298 ◽  
Author(s):  
K. D. Corbett ◽  
R. K. Shultzaberger ◽  
J. M. Berger
Keyword(s):  
Dna Bending ◽  
Dna Gyrase ◽  
Terminal Domain ◽  
Gyrase A

scholarly journals Cloning and nucleotide sequence of the gyrA gene from Campylobacter fetus subsp. fetus ATCC 27374 and characterization of ciprofloxacin-resistant laboratory and clinical isolates.

1997 ◽  
Vol 41 (3) ◽  
pp. 665-671 ◽  
Author(s):  
D E Taylor ◽  
A S Chau
Keyword(s):  
Nucleotide Sequence ◽  
Dna Gyrase ◽  
Amino Acid Identity ◽  
Gyra Gene ◽  
Reading Frame ◽  
B Subunit ◽  
Campylobacter Fetus ◽  
A Subunit ◽  
Fetus Subsp ◽  
Genomic Map

The gyrA gene of Campylobacter fetus subsp. fetus, which encodes the A subunit of DNA gyrase, was cloned, and its nucleotide sequence was determined. An open reading frame of 2,586 nucleotides which encodes a polypeptide of 862 amino acids with an Mr of 96,782 was identified. C. fetus subsp. fetus GyrA is most closely related to Campylobacter jejuni GyrA, with 73% homology at the nucleotide level and 78% identity between polypeptides. The next most closely related GyrA was that from Helicobacter pylori, with both DNA homology and amino acid identity of 63%. The gyrA and gyrB (DNA gyrase B subunit) genes were located on the genomic map of C. fetus subsp. fetus ATCC 27374 and shown to be separate. A clinical isolate of C. fetus subsp. fetus and a laboratory-derived mutant of ATCC 27374, both resistant to ciprofloxacin, had identical mutations within the quinolone resistance determining region. In both mutants a G-->T transversion, corresponding to a substitution of Asp-91 to Tyr in GyrA, was linked to ciprofloxacin resistance, giving MICs of 8 to 16 micrograms/ml.

4-(tert-butyl)-N,N-diethylbenzenesulfonamide: Structural, absorption distribution metabolism excretion toxicity (ADMET) and molecular docking studies

2021 ◽  
pp. 329-336 ◽  
Author(s):  
Gurumallappa Gurumallappa ◽  
Jayashankar Jayaprakash ◽  
Ananda A. Puttaswamy ◽  
Jayanth H. Sunderraj ◽  
Puttaswamappa Mallu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Title Compound ◽  
Living Organism ◽  
Dna Gyrase ◽  
Docking Studies ◽  
Monoclinic Crystal ◽  
Tert Butyl ◽  
B Subunit ◽  
A Subunit ◽  
Physical And Chemical

Sulfonamides are a very good antibacterial agent that targets essential bacterial enzymes specifically DNA gyrase. The objective of the present work was to investigate the molecular docking of the (4-(tert-butyl)-N,N-diethylbenzenesulfonamide) with the DNA gyrase of S. aureus. The energy-free topoisomerase activity of the A subunit, which breaks the DNA, is inhibited by 4-quilones such as nalidixic acid and ciprofloxacin. The energy transducing activity of the B subunit is inhibited by novobiocin and other coumarin antibiotics. Single crystal X-ray diffractometer study was carried out to understand the structure, physical and chemical reactive parameters, the title compound is crystallized under monoclinic crystal system with the space group of P21/C. To understand the behaviour of the title compound in living organism, Absorption, Distribution, Metabolism, Excretion analysis was done using Swiss ADME and Osiris data warrior tool. Further, Toxicity of the title compound was predicted by using PKCSM online software.

scholarly journals Disruption of the Borrelia burgdorferi gac Gene, Encoding the Naturally Synthesized GyrA C-Terminal Domain

2000 ◽  
Vol 182 (7) ◽  
pp. 2048-2051 ◽  
Author(s):  
Scott W. Knight ◽  
Betsy J. Kimmel ◽  
Christian H. Eggers ◽  
D. Scott Samuels
Keyword(s):  
Dna Binding ◽  
Borrelia Burgdorferi ◽  
Binding Protein ◽  
Dna Gyrase ◽  
Dna Binding Protein ◽  
Gene Encoding ◽  
Terminal Domain ◽  
A Subunit ◽  
Dna Maintenance ◽  
Independent Protein

ABSTRACT The C-terminal domain of the A subunit of DNA gyrase, which we term Gac, is naturally synthesized in Borrelia burgdorferi as an abundant DNA-binding protein. Full-length GyrA, which includes the C-terminal domain, is also synthesized by the spirochete and functions as a subunit of DNA gyrase. We have disrupted synthesis of Gac as an independent protein and demonstrated that it is not essential for growth in a coumarin-resistant background. We detected no alterations in DNA maintenance, condensation, or topology in B. burgdorferi lacking this small DNA-binding protein.

scholarly journals Purification, crystallization and preliminary X-ray crystallographic studies of theMycobacterium tuberculosisDNA gyrase CTD

2012 ◽  
Vol 68 (2) ◽  
pp. 178-180 ◽  
Author(s):  
Amélie Darmon ◽  
Jérémie Piton ◽  
Mélanie Roué ◽  
Stéphanie Petrella ◽  
Alexandra Aubry ◽  
...  
Keyword(s):  
Unique Feature ◽  
Dna Gyrase ◽  
Type Ii ◽  
Asymmetric Unit ◽  
X Ray Diffraction ◽  
Unique Type ◽  
X Ray ◽  
His Tag ◽  
Gyrase A ◽  
A Subunit

Mycobacterium tuberculosisDNA gyrase, a nanomachine involved in regulation of DNA topology, is the only type II topoisomerase present in this organism and hence is the sole target of fluoroquinolone in the treatment of tuberculosis. The C-terminal domain (CTD) of the DNA gyrase A subunit possesses a unique feature, the ability to wrap DNA in a chiral manner, that plays an essential role during the catalytic cycle. A construct of 36 kDa corresponding to this domain has been overproduced, purified and crystallized. Diffraction data were collected to 1.55 Å resolution. Cleavage of the N-terminal His tag was crucial for obtaining crystals. The crystals belonged to space groupP212121, with one molecule in the asymmetric unit and a low solvent content (33%). This is the first report of the crystallization and preliminary X-ray diffraction studies of a DNA gyrase CTD from a species that contains one unique type II topoisomerase.

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