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posted to fulllength sp thrmotoga topoisomerase
by Nambi
on 2006-04-09 17:34:45
Abstract
DNA topoisomerases are a family of enzymes altering the topology of DNA by concerted breakage and rejoining of the phosphodiester backbone of DNA. Bacterial and archeal type IA topoisomerases, including topoisomerase I, topoisomerase III, and reverse gyrase, are crucial in regulation of DNA supercoiling and maintenance of genetic stability. The crystal structure of full length topoisomerase I from Thermotoga maritima was determined at 1.7A resolution and represents an intact and fully active bacterial topoisomerase I. It reveals the torus-like structure of ...
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J Basic Microbiol, Vol. 37, No. 1. (1997), pp. 53-69
posted to no-tag
by Nambi
on 2006-03-10 19:22:58
Abstract
The intracellular level of DNA supercoiling is regulated in Escherichia coli by a homeostatic control mechanism that includes DNA gyrase and topoisomerase I gene expression. Despite several biochemical and genetical evidence that supports the existence of a homeostatic regulation mechanism, there are only few studies focusing gyrA and gyrB gene expression in connection to the mechanism involved in the regulation of DNA supercoiling in vivo. To study DNA gyrase gene expression and to be able to isolate mutants with altered expression ...
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Antimicrob Agents Chemother, Vol. 38, No. 9. (September 1994), pp. 1966-1973
posted to no-tag
by Nambi
on 2006-03-10 19:21:27
Abstract
We investigated how cyclothialidine (Ro 09-1437), a novel DNA gyrase inhibitor belonging to a new chemical class of compounds, acts to inhibit Escherichia coli DNA gyrase. Cyclothialidine up to 100 micrograms/ml showed no effect on DNA gyrase when linear DNA was used as a substrate. Under the same conditions, quinolones, which inhibit the resealing reaction of DNA gyrase, caused a decrease in the amount of linear DNA used. No effect of cyclothialidine was observed on the accumulation of the covalent complex ...
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Science, Vol. 207, No. 4434. (29 February 1980), pp. 953-960
posted to gyrase supercoilingdna
by Nambi
on 2006-03-06 17:31:59
Abstract
Negative supercoiling of bacterial DNA by DNA gyrase influences all metabolic processes involving DNA and is essential for replication. Gyrase supercoils DNA by a mechanism called sign inversion, whereby a positive supercoil is directly inverted to a negative one by passing a DNA segment through a transient double-strand break. Reversal of this scheme relaxes DNA, and this mechanism also accounts for the ability of gyrase to catenate and uncatenate DNA rings. Each round of supercoiling is driven by a conformational change ...
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Mol Biol (Mosk), Vol. 16, No. 5. (t 1982), pp. 1019-1025
posted to dna gyrase subunit
by Nambi
on 2006-03-06 17:25:46
Abstract
Interaction of DNA gyrase A- and B-subunits during the process of DNA supercoiling was studied. For this purpose a E. coli Cour-1 mutant resistant to coumermycin and containing a mutation in the B-subunit of DNA gyrase was isolated and the influence of the DNA gyrase A-subunit specific inhibitor-nalidixic acid-on DNA supercoiling by wild-type and mutant enzymes was investigated. It turned out that the enzyme from the Cour-1 mutant strain was more sensitive to nalidixic acid than the DNA gyrase from the ...
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posted to d8inhibitor dna gyrase simocyclinone
by Nambi
on 2006-03-05 03:13:39
Abstract
We have characterized the interaction of a new class of antibiotics, simocyclinones, with bacterial DNA gyrase. Even though their structures include an aminocoumarin moiety, a key feature of novobiocin, coumermycin A(1), and clorobiocin, which also target gyrase, simocyclinones behave strikingly differently from these compounds. Simocyclinone D8 is a potent inhibitor of gyrase supercoiling, with a 50% inhibitory concentration lower than that of novobiocin. However, it does not competitively inhibit the DNA-independent ATPase reaction of GyrB, which is characteristic of other aminocoumarins. ...
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Nippon Rinsho, Vol. 51, No. 12. (December 1993), pp. 3291-3300
posted to no-tag
by Nambi
on 2006-03-04 18:30:28
Abstract
DNA topoisomerases are enzymes involved in various aspects of genetic processes by catalyzing a topological change of DNA. Topoisomerase is now viewed as an important cellular target of antitumor drugs. These drugs targeting topoisomerase have been used to establish a relationship between drug-induced cleavable complex formation and cytotoxicity. Topoisomerase I is shown to be the cellular target of camptothecin and its derivatives. And topoisomerase II targeting drugs are both intercalative drugs (acridines, ellipticines, anthracyclines) and non-intercalative drugs (epipodophyllotoxin derivatives). And then ...
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Biochem Pharmacol, Vol. 54, No. 4. (15 August 1997), pp. 467-473
posted to no-tag
by Nambi
on 2006-03-04 18:29:10
Abstract
The cytotoxic oxoaporphine alkaloid liriodenine, isolated from Cananga odorata, was found to be a potent inhibitor of topoisomerase II (EC 5.99.1.3) both in vivo and in vitro. Liriodenine treatment of SV40 (simian virus 40)-infected CV-1 cells caused highly catenated SV40 daughter chromosomes, a signature of topoisomerase II inhibition. Strong catalytic inhibition of topoisomerase II by liriodenine was confirmed by in vitro assays with purified human topoisomerase II and kinetoplast DNA. Liriodenine also caused low-level protein-DNA cross-links to pulse-labeled SV40 chromosomes in ...
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Curr Opin Oncol, Vol. 5, No. 6. (November 1993), pp. 1023-1028
posted to dna inhibitors topoisomerase
by Nambi
on 2006-03-04 18:26:25
Abstract
The topology of DNA is regulated by DNA-topoisomerase enzymes, which induce either transient DNA single-strand breaks (topoisomerase I) or DNA double-strand breaks (topoisomerase II). The action of several anticancer drugs, eg, DNA intercalating agents (ie, anthracyclines, anthracenediones, anthrapyrazoles, amsacrines, and ellipticines) and epipodophyllotoxins, appears to be mediated by the enzyme topoisomerase II alpha. The action of camptothecins is mediated by topoisomerase I. All of these drugs cause the induction of DNA enzyme complexes. Some new topoisomerase inhibitors have instead the ability ...
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Proc Natl Acad Sci U S A, Vol. 93, No. 18. (3 September 1996), pp. 9477-9482
Abstract
A synthetic strand of RNA has been designed so that it can adopt two different topological states (a circle and a trefoil knot) when ligated into a cyclic molecule. The RNA knot and circle have been characterized by their behavior in gel electrophoresis and sedimentation experiments. This system allows one to assay for the existence of an RNA topoisomerase, because the two RNA molecules can be inter-converted only by a strand passage event. We find that the interconversion of these two ...
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Nucleic Acids Res, Vol. 28, No. 2. (15 January 2000), pp. 552-559
posted to no-tag
by Nambi
on 2006-03-04 13:09:08
Abstract
Genetic evidence suggests that the Bacillus subtilis lrpC gene product participates in cell growth and sporulation. The purified LrpC protein, which has a predicted molecular mass of 16.4 kDa, is a tetramer in solution. LrpC binds with higher affinity ( K (app) approximately 80 nM) to intrinsically curved DNA than to non-curved DNA ( K (app) approximately 700 nM). DNase I footprinting and the supercoiling of relaxed circular plasmid DNA in the presence of topoisomerase I revealed that LrpC induces DNA ...
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Methods Mol Biol, Vol. 95 (2001), pp. 25-33
posted to no-tag
by Nambi
on 2006-03-04 13:03:27
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posted to assay dna gyrase supercoiling
by Nambi
on 2006-03-04 12:42:24
Abstract
Reverse gyrase, the only topoisomerase known to positively supercoil DNA, has an N-terminal ATPase domain that drives the activity of a topoisomerase domain. This study shows that the N-terminal domain represses topoisomerase activity in the absence of nucleotide, and nucleotide binding is sufficient to relieve the repression. A "latch" region in the N-terminal part was observed to close over the topoisomerase domain in the reverse gyrase crystal structure. Mutants lacking all or part of the latch relax DNA in the absence ...
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Proceedings of the National Academy of Sciences of the United States of America, Vol. 73, No. 8. (August 1976), pp. 2639-2643
posted to no-tag
by Nambi
on 2006-02-17 12:30:47
along with 1 person
tictacgo
Abstract
In considering supercoils formed by closed double-stranded molecules of DNA certain mathematical concepts, such as the linking number and the twist, are needed. The meaning of these for a closed ribbon is explained and also that of the writhing number of a closed curve. Some simple examples are given, some of which may be relevant to the structure of chromatin. ...
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J Mol Biol, Vol. 129, No. 3. (15 April 1979), pp. 449-457
posted to no-tag
by Nambi
on 2006-02-17 12:30:18
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Nature reviews. Drug discovery, Vol. 1, No. 9. (01 September 2002), pp. 727-730, doi:10.1038/nrd892
Abstract
An assessment of the number of molecular targets that represent an opportunity for therapeutic intervention is crucial to the development of post-genomic research strategies within the pharmaceutical industry. Now that we know the size of the human genome, it is interesting to consider just how many molecular targets this opportunity represents. We start from the position that we understand the properties that are required for ...
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Abstract
Bacterial chromosomes are highly compacted structures and share many properties with their eukaryote counterparts, despite not being organized into chromatin or being contained within a cell nucleus. Proteins conserved across all branches of life act in chromosome organization, and common mechanisms maintain genome integrity and ensure faithful replication. The principles that underlie chromosome segregation in bacteria and eukaryotes share similarities, although bacteria segregate DNA as it replicates and lack a eukaryote-like mitotic apparatus for segregating chromosomes. This may be because the ...
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Expert Opin Ther Targets, Vol. 5, No. 4. (August 2001), pp. 531-533
posted to no-tag
by Nambi
on 2006-02-08 17:03:44
Abstract
The discovery of the peptide DNA gyrase inhibitor microcin B17 (MccB17) in the early 1990s provided a new tool and hope for a novel peptide-based chemical starting point for a new generation of DNA gyrase inhibitors but the definitive mechanism-of-action of MccB17 has remained unknown. This research report [1], by one of the foremost laboratories in this discipline in the world, provides definitive data on the mode of inhibition of MccB17 and possibly opens the door for additional semisynthetic analogue synthesis ...
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Rev Infect Dis, Vol. 11 Suppl 5 (g 1989)
posted to dna gyrase inhibitor
by Nambi
on 2006-02-08 16:47:50
Abstract
Since metabolites of gyrase inhibitors (including the quinolones) may contribute to or even determine the occurrence of adverse effects or interactions with other drugs, an understanding of even minor metabolic pathways is important. The extent of metabolism can be estimated by determination of the renal and nonrenal clearance of drug and by measurement of excretion of drug labeled with 14C. The principal metabolic pathways of gyrase inhibitors are piperazine ring-based reactions (formation of oxo-compounds, N-oxides, demethylation products where applicable, or ring ...
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Trends Microbiol, Vol. 5, No. 3. (March 1997), pp. 102-109
posted to dna drug gyrase review target
by Nambi
on 2006-02-08 13:39:45
Abstract
DNA gyrase is a remarkable enzyme, catalysing the seemingly complex reaction of DNA supercoiling. As gyrase is essential in prokaryotes, it is a good target for antibacterial agents. These agents have diverse chemical structures and interact with gyrase in a variety of ways. ...
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Biol Chem, Vol. 377, No. 7-8. (g 1996), pp. 465-470
Abstract
Trypsin and chymotrypsin have similar tertiary structures, although very different substrate specificities. Trypsin hydrolyzes peptides at Lys/Arg residues while chymotrypsin recognizes large hydrophobic residues. Recent work has shown that trypsin is not converted into a protease with chymotrypsin-like activity when the S1 substrate binding site residues are replaced with their chymotrypsin counterparts. Chymotrypsin-like activity is reconstituted in the trypsin framework when two surface loops are substituted with the analogous loops of chymotrypsin in addition to the substitutions at the S1 site. ...
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Abstract
Genome studies suggest that DNA gyrase is the sole type II topoisomerase and likely the unique target of quinolones in Mycobacterium tuberculosis. Despite the emerging importance of quinolones in the treatment of mycobacterial disease, the slow growth and high pathogenicity of M. tuberculosis have precluded direct purification of its gyrase and detailed analysis of quinolone action. To address these issues, we separately overexpressed the M. tuberculosis DNA gyrase GyrA and GyrB subunits as His-tagged proteins in Escherichia coli from pET plasmids ...
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posted to enzyme gyra gyrase mtb mutation
by Nambi
on 2006-01-20 21:38:08
Abstract
Mutations in the DNA gyrase GyrA2GyrB2 complex are associated with resistance to quinolones in Mycobacterium tuberculosis. As fluoroquinolones are being used increasingly in the treatment of tuberculosis, we characterized several multidrug-resistant clinical isolates of M. tuberculosis carrying mutations in the genes encoding the GyrA or GyrB subunits associated with quinolone resistance or hypersusceptibility. In addition to the reported putative quinolone resistance mutations in GyrA, i.e., A90V, D94G, and D94H, we found that the GyrB N510D mutation was also associated with ofloxacin ...
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Dis Aquat Organ, Vol. 67, No. 3. (28 November 2005), pp. 259-266
posted to cloning gyra gyrase
by Nambi
on 2006-01-20 21:16:52
Abstract
Knowing the entire sequence of the gene encoding the DNA gyrase Subunit A (gyrA) of Edwardsiella tarda could be very useful for confirming the role of gyrA in quinolone resistance. Degenerate primers for the amplification of gyrA were designed from consensus nucleotide sequences of gyrA from 9 different Gram-negative bacteria, including Escherichia coli. With these primers, DNA segments of the predicted size were amplified from the genomic DNA of E. tarda and then the flanking sequences were determined by cassette ligation-mediated ...
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