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PDBsum entry 1ab4
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Topoisomerase
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PDB id
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1ab4
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.5.6.2.2
- Dna topoisomerase (ATP-hydrolyzing).
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DOI no:
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Nature
388:903-906
(1997)
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PubMed id:
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Crystal structure of the breakage-reunion domain of DNA gyrase.
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J.H.Morais Cabral,
A.P.Jackson,
C.V.Smith,
N.Shikotra,
A.Maxwell,
R.C.Liddington.
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ABSTRACT
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DNA gyrase is a type II DNA topoisomerase from bacteria that introduces
supercoils into DNA. It catalyses the breakage of a DNA duplex (the G segment),
the passage of another segment (the T segment) through the break, and then the
reunification of the break. This activity involves the opening and dosing of a
series of molecular 'gates' which is coupled to ATP hydrolysis. Here we present
the crystal structure of the 'breakage-reunion' domain of the gyrase at 2.8 A
resolution. Comparison of the structure of this 59K (relative molecular mass,
59,000) domain with that of a 92K fragment of yeast topoisomerase II reveals a
very different quaternary organization, and we propose that the two structures
represent two principal conformations that participate in the enzymatic pathway.
The gyrase structure reveals a new dimer contact with a grooved concave surface
for binding the G segment and a cluster of conserved charged residues
surrounding the active-site tyrosines. It also shows how breakage of the G
segment can occur and, together with the topoisomerase II structure, suggests a
pathway by which the T segment can be released through the second gate of the
enzyme. Mutations that confer resistance to the quinolone antibacterial agents
cluster at the new dimer interface, indicating how these drugs might interact
with the gyrase-DNA complex.
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Selected figure(s)
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Figure 2.
Figure 2 a, b, Orthogonal views of GyrA59 and the yeast topo
II A' subunit. Head fragments are shown in blue,
helix-turn-helix motifs in yellow ( 3)
and red ( 4),
tail domains in grey, active-site tyrosines as green spheres.
Arrows show the direction of movement from topo II to gyrase. c,
Opening of the 'second gate' in the primary dimer interface (see
text). The A' subunits of yeast topo II were superimposed onto
the GyrA59 dimer structure by least-squares fits onto the 'head'
fragments. The view is rotated about a vertical axis to show the
full extent of the gate ( 22
?). d, Two conformations of the connecting helices, superimposed
at the 'primary' dimer interface. Arrows show the direction of
movement from topo II to gyrase.
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Figure 3.
Figure 3 a, GRASP22 electrostatic surface potential of the
GyrA59 dimer (orthogonal stereo views).: negatively charged
surfaces are in red, positively charged surfaces in blue. The
DNA backbone is shown as a green and red ribbon; active-site
tyrosines as yellow stars, target phosphoryl groups as yellow
dots. b, Close-up of the 'head' dimer interface (colour scheme
as in Fig. 2), with some secondary structure elements indicated.
Quinolone-resistance sites are shown as numbered black spheres.
c, Space-filling model, viewed as in b. Monomers are shown in
pale green and pink. Quinolone-resistance sites are in black.
Residues picked out in other colours are highly conserved within
the topoisomerase family.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(1997,
388,
903-906)
copyright 1997.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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B.H.Schmidt,
N.Osheroff,
and
J.M.Berger
(2012).
Structure of a topoisomerase II-DNA-nucleotide complex reveals a new control mechanism for ATPase activity.
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Nat Struct Mol Biol,
19,
1147-1154.
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PDB code:
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D.Klostermeier
(2011).
Single-molecule FRET reveals nucleotide-driven conformational changes in molecular machines and their link to RNA unwinding and DNA supercoiling.
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Biochem Soc Trans,
39,
611-616.
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N.M.Baker,
S.Weigand,
S.Maar-Mathias,
and
A.Mondragón
(2011).
Solution structures of DNA-bound gyrase.
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Nucleic Acids Res,
39,
755-766.
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S.Heeb,
M.P.Fletcher,
S.R.Chhabra,
S.P.Diggle,
P.Williams,
and
M.Cámara
(2011).
Quinolones: from antibiotics to autoinducers.
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FEMS Microbiol Rev,
35,
247-274.
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X.Xiong,
E.H.Bromley,
P.Oelschlaeger,
D.N.Woolfson,
and
J.Spencer
(2011).
Structural insights into quinolone antibiotic resistance mediated by pentapeptide repeat proteins: conserved surface loops direct the activity of a Qnr protein from a Gram-negative bacterium.
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Nucleic Acids Res,
39,
3917-3927.
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PDB codes:
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A.J.Schoeffler,
A.P.May,
and
J.M.Berger
(2010).
A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a critical role in gyrase function.
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Nucleic Acids Res,
38,
7830-7844.
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PDB code:
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B.D.Bax,
P.F.Chan,
D.S.Eggleston,
A.Fosberry,
D.R.Gentry,
F.Gorrec,
I.Giordano,
M.M.Hann,
A.Hennessy,
M.Hibbs,
J.Huang,
E.Jones,
J.Jones,
K.K.Brown,
C.J.Lewis,
E.W.May,
M.R.Saunders,
O.Singh,
C.E.Spitzfaden,
C.Shen,
A.Shillings,
A.J.Theobald,
A.Wohlkonig,
N.D.Pearson,
and
M.N.Gwynn
(2010).
Type IIA topoisomerase inhibition by a new class of antibacterial agents.
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Nature,
466,
935-940.
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PDB codes:
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B.H.Schmidt,
A.B.Burgin,
J.E.Deweese,
N.Osheroff,
and
J.M.Berger
(2010).
A novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases.
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Nature,
465,
641-644.
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PDB codes:
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C.Sissi,
and
M.Palumbo
(2010).
In front of and behind the replication fork: bacterial type IIA topoisomerases.
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Cell Mol Life Sci,
67,
2001-2024.
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I.Vranakis,
V.Sandalakis,
D.Chochlakis,
Y.Tselentis,
and
A.Psaroulaki
(2010).
DNA gyrase and topoisomerase IV mutations in an in vitro fluoroquinolone-resistant Coxiella burnetii strain.
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Microb Drug Resist,
16,
111-117.
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J.Piton,
S.Petrella,
M.Delarue,
G.André-Leroux,
V.Jarlier,
A.Aubry,
and
C.Mayer
(2010).
Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase.
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PLoS One,
5,
e12245.
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PDB codes:
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J.Yuan,
Y.Sterckx,
L.A.Mitchenall,
A.Maxwell,
R.Loris,
and
M.K.Waldor
(2010).
Vibrio cholerae ParE2 poisons DNA gyrase via a mechanism distinct from other gyrase inhibitors.
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J Biol Chem,
285,
40397-40408.
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M.A.Kohanski,
D.J.Dwyer,
and
J.J.Collins
(2010).
How antibiotics kill bacteria: from targets to networks.
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Nat Rev Microbiol,
8,
423-435.
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P.Xie
(2010).
Dynamics of strand passage catalyzed by topoisomerase II.
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Eur Biophys J,
39,
1251-1259.
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Q.Guo,
J.Weng,
X.Xu,
M.Wang,
X.Wang,
X.Ye,
W.Wang,
and
M.Wang
(2010).
A mutational analysis and molecular dynamics simulation of quinolone resistance proteins QnrA1 and QnrC from Proteus mirabilis.
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BMC Struct Biol,
10,
33.
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A.Gubaev,
M.Hilbert,
and
D.Klostermeier
(2009).
The DNA-gate of Bacillus subtilis gyrase is predominantly in the closed conformation during the DNA supercoiling reaction.
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Proc Natl Acad Sci U S A,
106,
13278-13283.
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A.Mérens,
S.Matrat,
A.Aubry,
C.Lascols,
V.Jarlier,
C.J.Soussy,
J.D.Cavallo,
and
E.Cambau
(2009).
The pentapeptide repeat proteins MfpAMt and QnrB4 exhibit opposite effects on DNA gyrase catalytic reactions and on the ternary gyrase-DNA-quinolone complex.
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J Bacteriol,
191,
1587-1594.
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G.Fu,
J.Wu,
D.Zhu,
Y.Hu,
L.Bi,
X.E.Zhang,
and
d.a. .C.Wang
(2009).
Crystallization and preliminary crystallographic studies of Mycobacterium tuberculosis DNA gyrase B C-terminal domain, part of the enzyme reaction core.
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
65,
350-352.
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G.Fu,
J.Wu,
W.Liu,
D.Zhu,
Y.Hu,
J.Deng,
X.E.Zhang,
L.Bi,
and
D.C.Wang
(2009).
Crystal structure of DNA gyrase B' domain sheds lights on the mechanism for T-segment navigation.
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Nucleic Acids Res,
37,
5908-5916.
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PDB code:
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L.Nguyen,
and
J.Pieters
(2009).
Mycobacterial subversion of chemotherapeutic reagents and host defense tactics: challenges in tuberculosis drug development.
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Annu Rev Pharmacol Toxicol,
49,
427-453.
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M.J.Edwards,
R.H.Flatman,
L.A.Mitchenall,
C.E.Stevenson,
T.B.Le,
T.A.Clarke,
A.R.McKay,
H.P.Fiedler,
M.J.Buttner,
D.M.Lawson,
and
A.Maxwell
(2009).
A crystal structure of the bifunctional antibiotic simocyclinone d8, bound to DNA gyrase.
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Science,
326,
1415-1418.
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PDB codes:
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M.L.Beeton,
V.J.Chalker,
N.C.Maxwell,
S.Kotecha,
and
O.B.Spiller
(2009).
Concurrent titration and determination of antibiotic resistance in ureaplasma species with identification of novel point mutations in genes associated with resistance.
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Antimicrob Agents Chemother,
53,
2020-2027.
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M.Simic,
N.De Jonge,
R.Loris,
G.Vesnaver,
and
J.Lah
(2009).
Driving forces of gyrase recognition by the addiction toxin CcdB.
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J Biol Chem,
284,
20002-20010.
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N.De Jonge,
A.Garcia-Pino,
L.Buts,
S.Haesaerts,
D.Charlier,
K.Zangger,
L.Wyns,
H.De Greve,
and
R.Loris
(2009).
Rejuvenation of CcdB-poisoned gyrase by an intrinsically disordered protein domain.
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Mol Cell,
35,
154-163.
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PDB codes:
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X.S.Pan,
K.A.Gould,
and
L.M.Fisher
(2009).
Probing the differential interactions of quinazolinedione PD 0305970 and quinolones with gyrase and topoisomerase IV.
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Antimicrob Agents Chemother,
53,
3822-3831.
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A.J.Schoeffler,
and
J.M.Berger
(2008).
DNA topoisomerases: harnessing and constraining energy to govern chromosome topology.
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Q Rev Biophys,
41,
41.
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K.Drlica,
M.Malik,
R.J.Kerns,
and
X.Zhao
(2008).
Quinolone-mediated bacterial death.
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Antimicrob Agents Chemother,
52,
385-392.
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L.Balsalobre,
and
A.G.de la Campa
(2008).
Fitness of Streptococcus pneumoniae fluoroquinolone-resistant strains with topoisomerase IV recombinant genes.
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Antimicrob Agents Chemother,
52,
822-830.
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M.T.Black,
T.Stachyra,
D.Platel,
A.M.Girard,
M.Claudon,
J.M.Bruneau,
and
C.Miossec
(2008).
Mechanism of action of the antibiotic NXL101, a novel nonfluoroquinolone inhibitor of bacterial type II topoisomerases.
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Antimicrob Agents Chemother,
52,
3339-3349.
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S.M.Hashimi,
G.Huang,
A.Maxwell,
and
R.G.Birch
(2008).
DNA gyrase from the albicidin producer Xanthomonas albilineans has multiple-antibiotic-resistance and unusual enzymatic properties.
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Antimicrob Agents Chemother,
52,
1382-1390.
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S.Matrat,
A.Aubry,
C.Mayer,
V.Jarlier,
and
E.Cambau
(2008).
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.
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Antimicrob Agents Chemother,
52,
2909-2914.
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X.S.Pan,
M.Dias,
M.Palumbo,
and
L.M.Fisher
(2008).
Clerocidin selectively modifies the gyrase-DNA gate to induce irreversible and reversible DNA damage.
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Nucleic Acids Res,
36,
5516-5529.
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D.A.Ostrov,
J.A.Hernández Prada,
P.E.Corsino,
K.A.Finton,
N.Le,
and
T.C.Rowe
(2007).
Discovery of novel DNA gyrase inhibitors by high-throughput virtual screening.
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Antimicrob Agents Chemother,
51,
3688-3698.
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F.Mueller-Planitz,
and
D.Herschlag
(2007).
DNA topoisomerase II selects DNA cleavage sites based on reactivity rather than binding affinity.
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Nucleic Acids Res,
35,
3764-3773.
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I.Laponogov,
D.A.Veselkov,
M.K.Sohi,
X.S.Pan,
A.Achari,
C.Yang,
J.D.Ferrara,
L.M.Fisher,
and
M.R.Sanderson
(2007).
Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target.
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PLoS ONE,
2,
e301.
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PDB code:
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J.Lipfert,
and
S.Doniach
(2007).
Small-angle X-ray scattering from RNA, proteins, and protein complexes.
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Annu Rev Biophys Biomol Struct,
36,
307-327.
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K.C.Dong,
and
J.M.Berger
(2007).
Structural basis for gate-DNA recognition and bending by type IIA topoisomerases.
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Nature,
450,
1201-1205.
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PDB code:
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K.Champion,
and
N.P.Higgins
(2007).
Growth rate toxicity phenotypes and homeostatic supercoil control differentiate Escherichia coli from Salmonella enterica serovar Typhimurium.
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J Bacteriol,
189,
5839-5849.
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K.D.Corbett,
P.Benedetti,
and
J.M.Berger
(2007).
Holoenzyme assembly and ATP-mediated conformational dynamics of topoisomerase VI.
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Nat Struct Mol Biol,
14,
611-619.
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PDB code:
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L.Cao,
H.Lin,
and
V.M.Mirsky
(2007).
Detection of antibiotics in food: extraction of fluoroquinolones by DNA.
|
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Anal Bioanal Chem,
388,
253-258.
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L.Costenaro,
J.G.Grossmann,
C.Ebel,
and
A.Maxwell
(2007).
Modular structure of the full-length DNA gyrase B subunit revealed by small-angle X-ray scattering.
|
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Structure,
15,
329-339.
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Y.Maeda,
A.Kiba,
K.Ohnishi,
and
Y.Hikichi
(2007).
Amino acid substitutions in GyrA of Burkholderia glumae are implicated in not only oxolinic acid resistance but also fitness on rice plants.
|
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Appl Environ Microbiol,
73,
1114-1119.
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A.Aubry,
N.Veziris,
E.Cambau,
C.Truffot-Pernot,
V.Jarlier,
and
L.M.Fisher
(2006).
Novel gyrase mutations in quinolone-resistant and -hypersusceptible clinical isolates of Mycobacterium tuberculosis: functional analysis of mutant enzymes.
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Antimicrob Agents Chemother,
50,
104-112.
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A.B.Smith,
and
A.Maxwell
(2006).
A strand-passage conformation of DNA gyrase is required to allow the bacterial toxin, CcdB, to access its binding site.
|
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Nucleic Acids Res,
34,
4667-4676.
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A.Robicsek,
G.A.Jacoby,
and
D.C.Hooper
(2006).
The worldwide emergence of plasmid-mediated quinolone resistance.
|
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Lancet Infect Dis,
6,
629-640.
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G.E.Schmitz,
and
D.M.Downs
(2006).
An allele of gyrA prevents Salmonella enterica serovar Typhimurium from using succinate as a carbon source.
|
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J Bacteriol,
188,
3126-3129.
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G.W.Buchko,
H.Robinson,
S.Ni,
H.B.Pakrasi,
and
M.A.Kennedy
(2006).
Cloning, expression, crystallization and preliminary crystallographic analysis of a pentapeptide-repeat protein (Rfr23) from the bacterium Cyanothece 51142.
|
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Acta Crystallogr Sect F Struct Biol Cryst Commun,
62,
1251-1254.
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G.W.Buchko,
S.Ni,
H.Robinson,
E.A.Welsh,
H.B.Pakrasi,
and
M.A.Kennedy
(2006).
Characterization of two potentially universal turn motifs that shape the repeated five-residues fold--crystal structure of a lumenal pentapeptide repeat protein from Cyanothece 51142.
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Protein Sci,
15,
2579-2595.
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PDB codes:
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J.Strahilevitz,
A.Robicsek,
and
D.C.Hooper
(2006).
Role of the extended alpha4 domain of Staphylococcus aureus gyrase A protein in determining low sensitivity to quinolones.
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Antimicrob Agents Chemother,
50,
600-606.
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M.Malik,
X.Zhao,
and
K.Drlica
(2006).
Lethal fragmentation of bacterial chromosomes mediated by DNA gyrase and quinolones.
|
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Mol Microbiol,
61,
810-825.
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M.Oram,
A.A.Travers,
A.J.Howells,
A.Maxwell,
and
M.L.Pato
(2006).
Dissection of the bacteriophage Mu strong gyrase site (SGS): significance of the SGS right arm in Mu biology and DNA gyrase mechanism.
|
| |
J Bacteriol,
188,
619-632.
|
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M.W.Vetting,
S.S.Hegde,
J.E.Fajardo,
A.Fiser,
S.L.Roderick,
H.E.Takiff,
and
J.S.Blanchard
(2006).
Pentapeptide repeat proteins.
|
| |
Biochemistry,
45,
1.
|
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S.B.Carr,
G.Makris,
S.E.Phillips,
and
C.D.Thomas
(2006).
Crystallization and preliminary X-ray diffraction analysis of two N-terminal fragments of the DNA-cleavage domain of topoisomerase IV from Staphylococcus aureus.
|
| |
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PDB code:
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PDB code:
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PDB code:
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DNA gyrase and topoisomerase IV are dual targets of clinafloxacin action in Streptococcus pneumoniae.
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Antimicrob Agents Chemother,
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|
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|
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Where a reference describes a PDB structure, the PDB
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');
}
}
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