Two short peptides including segments of subunit A of Escherichia coli DNA gyrase as potential probes to evaluate the antibacterial activity of quinolones

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorMarchetto, Reinaldo
dc.creatorNicolás, Ernesto
dc.creatorCastillo, Núria
dc.creatorBacardit, Jordi
dc.creatorNavia, Margarita
dc.creatorVila, Jordi
dc.creatorGiralt, Ernest
dc.date2014-05-27T11:20:15Z
dc.date2016-10-25T18:16:58Z
dc.date2014-05-27T11:20:15Z
dc.date2016-10-25T18:16:58Z
dc.date2001-03-10
dc.date.accessioned2017-04-06T00:59:15Z
dc.date.available2017-04-06T00:59:15Z
dc.identifierJournal of Peptide Science, v. 7, n. 1, p. 27-40, 2001.
dc.identifier1075-2617
dc.identifierhttp://hdl.handle.net/11449/66474
dc.identifierhttp://acervodigital.unesp.br/handle/11449/66474
dc.identifier10.1002/psc.292
dc.identifierWOS:000167223300004
dc.identifier2-s2.0-0035109610
dc.identifierhttp://dx.doi.org/10.1002/psc.292
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/888040
dc.descriptionQuinolones constitute a family of compounds with a potent antibiotic activity. The enzyme DNA gyrase, responsible for the replication and transcription processes in DNA of bacteria, is involved in the mechanism of action of these drugs. In this sense, it is believed that quinolones stabilize the so-called 'cleavable complex' formed by DNA and gyrase, but the whole process is still far from being understood at the molecular level. This information is crucial in order to design new biological active products. As an approach to the problem, we have designed and synthesized low molecular weight peptide mimics of DNA gyrase. These peptides correspond to sequences of the subunit A of the enzyme from Escherichia coli, that include the quinolone resistance-determining region (positions 75-92) and a segment containing the catalytic Tyr-122 (positions 116-130). The peptide mimic of the non-mutated enzyme binds to ciprofloxin (CFX) only when DNA and Mg2+ were present (Kd = 1.6 × 10 -6 m), a result previously found with DNA gyrase. On the other hand, binding was reduced when mutations of Ser-83 to Leu-83 and Asp-87 to Asn-87 were introduced, a double change previously found in the subunit A of DNA gyrase from several CFX-resistant clinical isolates of E. coli. These results suggest that synthetic peptides designed in a similar way to that described here can be used as mimics of gyrases (topoisomerases) in order to study the binding of the quinolone to the enzyme-DNA complex as well as the mechanism of action of these antibiotics. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd.
dc.languageeng
dc.relationJournal of Peptide Science
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAffinity chromatography
dc.subjectDNA gyrase
dc.subjectEscherichia coli
dc.subjectPeptide design
dc.subjectPeptide synthesis
dc.subjectQuinolones
dc.subjectSolid phase
dc.subjectTopoisomerases
dc.subjectasparagine
dc.subjectaspartic acid
dc.subjectbacterial DNA
dc.subjectbacterial enzyme
dc.subjectciprofloxacin
dc.subjectDNA topoisomerase (ATP hydrolysing)
dc.subjectleucine
dc.subjectmagnesium ion
dc.subjectquinolone derivative
dc.subjectserine
dc.subjectsynthetic peptide
dc.subjecttyrosine
dc.subjectalpha chain
dc.subjectamino acid sequence
dc.subjectantibacterial activity
dc.subjectantimicrobial activity
dc.subjectbacterium isolate
dc.subjectcatalysis
dc.subjectDNA replication
dc.subjectDNA transcription
dc.subjectdrug binding
dc.subjectdrug design
dc.subjectdrug mechanism
dc.subjectdrug resistance
dc.subjectdrug synthesis
dc.subjectenzyme subunit
dc.subjectgene mutation
dc.subjectmolecular biology
dc.subjectmolecular mimicry
dc.subjectmolecular weight
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectAnti-Infective Agents
dc.subjectBinding Sites
dc.subjectChromatography, Affinity
dc.subjectCiprofloxacin
dc.subjectDNA Topoisomerases, Type II
dc.subjectDrug Design
dc.subjectMolecular Probes
dc.subjectMutation
dc.subjectPeptides
dc.subjectSpectrometry, Fluorescence
dc.titleTwo short peptides including segments of subunit A of Escherichia coli DNA gyrase as potential probes to evaluate the antibacterial activity of quinolones
dc.typeOtro


Este ítem pertenece a la siguiente institución