Structural highlights
Function
A9J7N5_PREIN
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Prevotella intermedia is a major periodontopathogen contributing to human gingivitis and periodontitis. Such pathogens release proteases as virulence factors that cause deterrence of host defenses and tissue destruction. A new cysteine protease from the cysteine-histidine-dyad class, interpain A, was studied in its zymogenic and self-processed mature forms. 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 20A 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.
A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A.,Mallorqui-Fernandez N, Manandhar SP, Mallorqui-Fernandez G, Uson I, Wawrzonek K, Kantyka T, Sola M, Thogersen IB, Enghild JJ, Potempa J, Gomis-Ruth FX J Biol Chem. 2008 Feb 1;283(5):2871-82. Epub 2007 Nov 9. PMID:17993455[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mallorqui-Fernandez N, Manandhar SP, Mallorqui-Fernandez G, Uson I, Wawrzonek K, Kantyka T, Sola M, Thogersen IB, Enghild JJ, Potempa J, Gomis-Ruth FX. A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A. J Biol Chem. 2008 Feb 1;283(5):2871-82. Epub 2007 Nov 9. PMID:17993455 doi:10.1074/jbc.M708481200