English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/107909
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:


Three-dimensional structure of MecI. Molecular basis for transcriptional regulation of staphylococcal methicillin resistance

AuthorsGarcía-Castellanos, Raquel; Marrero, Aniebrys ; Mallorquí-Fernández, Goretti; Potempa, Jan; Coll, Miquel ; Gomis-Rüth, F. Xavier
Issue Date24-Jul-2003
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationJournal of Biological Chemistry 278(41): 39897-39905 (2003)
AbstractMethicillin-resistant Staphylococcus aureus is the main cause of nosocomial and community-onset infections that affect millions of people worldwide. Some methicillin-resistant Staphylococcus aureus infections have become essentially untreatable by β-lactams because of acquired molecular machineries enabling antibiotic resistance. Evasion from methicillin challenge is mainly achieved by the synthesis of a penicillin-binding protein of low affinity for antibiotics, MecA, that replaces regular penicillin-binding proteins in cell wall turnover when these have been inactivated by antibiotics. MecA synthesis is regulated by a signal transduction system consisting of the sensor/transducer MecR1 and the 14-kDa transcriptional repressor MecI (also known as methicillin repressor) that constitutively blocks mecA transcription. The three-dimensional structure of MecI reveals a dimer of two independent winged helix domains, each of which binds a palindromic DNA-operator half site, and two intimately intertwining dimerization domains of novel spiral staircase architecture, held together by a hydrophobic core. Limited proteolytic cleavage by cognate MecR1 within the dimerization domains results in loss of dimer interaction surface, dissociation, and repressor release, which triggers MecA synthesis. Structural information on components of the MecA regulatory pathway, in particular on methicillin repressor, the ultimate transcriptional trigger of mecA-encoded methicillin resistance, is expected to lead to the development of new antimicrobial drugs.
Publisher version (URL)http://dx.doi.org/10.1074/jbc.M307199200
Identifiersdoi: 10.1074/jbc.M307199200
issn: 0021-9258
Appears in Collections:(IBMB) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
Show full item record
Review this work

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.