A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A

20 pages, 5 figures, 2 tables.-- PMID: 17993455 [PubMed].-- PMCID: PMC2772895.-- NIHMSID: NIHMS65935.-- Available online Nov 7, 2007.

Bibliographic Details
Authors: Mallorquí-Fernández, Noemí, Manandhar, Surya P., Mallorquí-Fernández, Goretti, Usón, Isabel, Wawrzonek, Katarzyna, Kantyka, Tomasz, Solà, Maria, Thøgersen, Ida B., Enghild, Jan J., Potempa, Jan, Gomis-Rüth, F. Xavier
Format: article
Publication Date:2008
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/25353
Online Access:http://hdl.handle.net/10261/25353
Access Level:Open access
Keyword:Periodontal disease
Prevotella intermedia
Bacterial periodontal pathogen
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spelling A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain AMallorquí-Fernández, NoemíManandhar, Surya P.Mallorquí-Fernández, GorettiUsón, IsabelWawrzonek, KatarzynaKantyka, TomaszSolà, MariaThøgersen, Ida B.Enghild, Jan J.Potempa, JanGomis-Rüth, F. XavierPeriodontal diseasePrevotella intermediaBacterial periodontal pathogen20 pages, 5 figures, 2 tables.-- PMID: 17993455 [PubMed].-- PMCID: PMC2772895.-- NIHMSID: NIHMS65935.-- Available online Nov 7, 2007.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.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.Peer reviewedAmerican Society for Biochemistry and Molecular Biology201020102008info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_65014326569 bytesapplication/pdfhttp://hdl.handle.net/10261/25353reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1074/jbc.M708481200info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/253532026-05-22T06:33:51Z
dc.title.none.fl_str_mv A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A
title A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A
spellingShingle A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A
Mallorquí-Fernández, Noemí
Periodontal disease
Prevotella intermedia
Bacterial periodontal pathogen
title_short A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A
title_full A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A
title_fullStr A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A
title_full_unstemmed A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A
title_sort A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A
dc.creator.none.fl_str_mv Mallorquí-Fernández, Noemí
Manandhar, Surya P.
Mallorquí-Fernández, Goretti
Usón, Isabel
Wawrzonek, Katarzyna
Kantyka, Tomasz
Solà, Maria
Thøgersen, Ida B.
Enghild, Jan J.
Potempa, Jan
Gomis-Rüth, F. Xavier
author Mallorquí-Fernández, Noemí
author_facet Mallorquí-Fernández, Noemí
Manandhar, Surya P.
Mallorquí-Fernández, Goretti
Usón, Isabel
Wawrzonek, Katarzyna
Kantyka, Tomasz
Solà, Maria
Thøgersen, Ida B.
Enghild, Jan J.
Potempa, Jan
Gomis-Rüth, F. Xavier
author_role author
author2 Manandhar, Surya P.
Mallorquí-Fernández, Goretti
Usón, Isabel
Wawrzonek, Katarzyna
Kantyka, Tomasz
Solà, Maria
Thøgersen, Ida B.
Enghild, Jan J.
Potempa, Jan
Gomis-Rüth, F. Xavier
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Periodontal disease
Prevotella intermedia
Bacterial periodontal pathogen
topic Periodontal disease
Prevotella intermedia
Bacterial periodontal pathogen
description 20 pages, 5 figures, 2 tables.-- PMID: 17993455 [PubMed].-- PMCID: PMC2772895.-- NIHMSID: NIHMS65935.-- Available online Nov 7, 2007.
publishDate 2008
dc.date.none.fl_str_mv 2008
2010
2010
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/25353
url http://hdl.handle.net/10261/25353
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1074/jbc.M708481200
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 4326569 bytes
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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