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Título

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

AutorMallorquí-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
Palabras clavePeriodontal disease
Prevotella intermedia
Bacterial periodontal pathogen
Fecha de publicación1-feb-2008
EditorAmerican Society for Biochemistry and Molecular Biology
CitaciónJournal of Biological Chemistry 283(5): 2871–2882 (2008)
ResumenPrevotella 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.
Descripción20 pages, 5 figures, 2 tables.-- PMID: 17993455 [PubMed].-- PMCID: PMC2772895.-- NIHMSID: NIHMS65935.-- Available online Nov 7, 2007.
Versión del editorhttp://dx.doi.org/10.1074/jbc.M708481200
URIhttp://hdl.handle.net/10261/25353
DOI10.1074/jbc.M708481200
ISSN0021-9258 (Print)
1083-351X (Online)
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