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dc.contributor.author | Mallorquí-Fernández, Noemí | - |
dc.contributor.author | Manandhar, Surya P. | - |
dc.contributor.author | Mallorquí-Fernández, Goretti | - |
dc.contributor.author | Usón, Isabel | - |
dc.contributor.author | Wawrzonek, Katarzyna | - |
dc.contributor.author | Kantyka, Tomasz | - |
dc.contributor.author | Solà, Maria | - |
dc.contributor.author | Thøgersen, Ida B. | - |
dc.contributor.author | Enghild, Jan J. | - |
dc.contributor.author | Potempa, Jan | - |
dc.contributor.author | Gomis-Rüth, F. Xavier | - |
dc.date.accessioned | 2010-06-17T08:02:55Z | - |
dc.date.available | 2010-06-17T08:02:55Z | - |
dc.date.issued | 2008-02-01 | - |
dc.identifier.citation | Journal of Biological Chemistry 283(5): 2871–2882 (2008) | en_US |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/10261/25353 | - |
dc.description | 20 pages, 5 figures, 2 tables.-- PMID: 17993455 [PubMed].-- PMCID: PMC2772895.-- NIHMSID: NIHMS65935.-- Available online Nov 7, 2007. | en_US |
dc.description.abstract | Prevotella intermedia is a major periodontopathogen contributing to human gingivitis and periodontitis. Such pathogens release proteases as virulence factors that cause deterrence of host defences and tissue destruction. A new cysteine protease from the cysteine-histidine-dyad class, interpain A, was studied in its zymogenic and its self-processed mature form. The latter consists of a bivalved moiety made up by two subdomains. In the structure of a catalytic cysteine-to-alanine zymogen variant, the right subdomain interacts with an unusual prodomain, thus contributing to latency. Unlike the catalytic cysteine residue, already in its competent conformation in the zymogen, the catalytic histidine is swung out from its active conformation and trapped in a cage shaped by a backing helix, a zymogenic hairpin and a latency flap in the zymogen. Dramatic rearrangement of up to 20Å of these elements triggered by a tryptophan switch occurs during activation and accounts for a new activation mechanism for proteolytic enzymes. These findings can be extrapolated to related potentially pathogenic cysteine proteases such as Streprococcus pyogenes SpeB and Porphyromonas gingivalis periodontain. | en_US |
dc.description.sponsorship | This study was supported by the following grants: BIO2004-20369-E and BIO2003-06653 from the former Spanish Ministry for Science and Technology; BIO2006-02668, BIO2006-14139, BFU2006-09593 and CONSOLIDER-INGENIO 2010 Project “La Factoría de Cristalización” (CSD2006-00015) from the Spanish Ministry for Education and Science; EU FP6 Integrated Project LSHC-CT-2003-503297 “CANCERDEGRADOME”; EU FP6 Strep Project 18830 “CAMP”; and by “AVON-Project” 2005X0648 from the Spanish Association Against Cancer. Additional funding was obtained by J.J.E. from the Danish National Science Research Council and by J.P. from MNiSW (Warsaw, Poland) and an NIH grant DE 09761. Funding for synchrotron diffraction data collection was provided by the European Synchrotron Radiation Facility and the European Union. | en_US |
dc.format.extent | 4326569 bytes | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | en_US |
dc.publisher | American Society for Biochemistry and Molecular Biology | en_US |
dc.rights | openAccess | en_US |
dc.subject | Periodontal disease | en_US |
dc.subject | Prevotella intermedia | en_US |
dc.subject | Bacterial periodontal pathogen | en_US |
dc.title | A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A | en_US |
dc.type | artículo | en_US |
dc.identifier.doi | 10.1074/jbc.M708481200 | - |
dc.description.peerreviewed | Peer reviewed | en_US |
dc.relation.publisherversion | http://dx.doi.org/10.1074/jbc.M708481200 | en_US |
dc.identifier.e-issn | 1083-351X | - |
dc.identifier.pmid | 17993455 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | With Fulltext | - |
item.languageiso639-1 | en | - |
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