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http://purl.uniprot.org/citations/24799625http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24799625http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24799625http://www.w3.org/2000/01/rdf-schema#comment"Streptococcal cysteine protease (SpeB), the major secreted protease produced by group A streptococcus (GAS), cleaves both host and bacterial proteins and contributes importantly to the pathogenesis of invasive GAS infections. Modulation of SpeB expression and/or its activity during invasive GAS infections has been shown to affect bacterial virulence and infection severity. Expression of SpeB is regulated by the GAS CovR-CovS two-component regulatory system, and we demonstrated that bacteria with mutations in the CovR-CovS two-component regulatory system are selected for during localized GAS infections and that these bacteria lack SpeB expression and exhibit a hypervirulent phenotype. Additionally, in a separate study, we showed that expression of SpeB can also be modulated by human transferrin-and/or lactoferrin-mediated iron chelation. Accordingly, the goal of this study was to investigate the possible roles of iron and other metals in modulating SpeB expression and/or activity in a manner that would potentiate bacterial virulence. Here, we report that the divalent metals zinc and copper inhibit SpeB activity at the posttranslational level. Utilizing online metal-binding site prediction servers, we identified two putative metal-binding sites in SpeB, one of which involves the catalytic-dyad residues (47)Cys and (195)His. Based on our findings, we propose that zinc and/or copper availability in the bacterial microenvironment can modulate the proteolytic activity of SpeB in a manner that preserves the integrity of several other virulence factors essential for bacterial survival and dissemination within the host and thereby may exacerbate the severity of invasive GAS infections."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.org/dc/terms/identifier"doi:10.1128/iai.01770-14"xsd:string
http://purl.uniprot.org/citations/24799625http://purl.org/dc/terms/identifier"doi:10.1128/iai.01770-14"xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/author"Caruso J.A."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/author"Caruso J.A."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/author"Chella Krishnan K."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/author"Chella Krishnan K."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/author"Kotb M."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/author"Kotb M."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/author"Landero Figueroa J.A."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/author"Landero Figueroa J.A."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/author"Mukundan S."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/author"Mukundan S."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/name"Infect. Immun."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/name"Infect. Immun."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/pages"2992-3001"xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/pages"2992-3001"xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/title"Metal-mediated modulation of streptococcal cysteine protease activity and its biological implications."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/title"Metal-mediated modulation of streptococcal cysteine protease activity and its biological implications."xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/volume"82"xsd:string
http://purl.uniprot.org/citations/24799625http://purl.uniprot.org/core/volume"82"xsd:string