@article{00550300b73311debc73000ea68e967b,
title = "Structure of the Mature Streptococcal Cysteine Protease Exotoxin mSpeB in Its Active Dimeric Form",
abstract = "Invasive infections of Streptococcus pyogenes are dependent on the cysteine protease streptococcal pyrogenic exotoxin B. Previous structures of the enzyme have not disclosed the proper active-site configuration. Here, the crystal structure of the mature enzyme is presented to 1.55 A, disclosing a homodimer. A serine from one subunit inserts into the active site of the other to donate to the oxyanion hole and coordinates the ligand proximal to the active-site cysteine. Dimerization is unique to the mature form and is clearly a prerequisite for catalysis. The present structure supports a tripartite switch system that is triggered upon dimerization and substrate binding: (1) liberation of the active-site histidine from an inactive configuration, (2) relocation of residues blocking the substrate binding pockets and (3) repositioning of two active-site tryptophans to settle in the active configuration. Based on the present structure, the active site of clan CA cysteine proteases is expanded and a detailed mechanism of the deacylation mechanism is proposed. The results may have applications for the development of protease inhibitors specific to bacterial cysteine proteases.",
author = "Olsen, {Johan G} and Robert Dagil and Niclasen, {Louise Meinert} and S{\o}rensen, {Ole E} and Kragelund, {Birthe B}",
note = "Keywords: catalytic mechanism; exotoxin; papain; Streptococcus pyogenes; Velcro loop",
year = "2009",
doi = "10.1016/j.jmb.2009.08.046",
language = "English",
volume = "393",
pages = "693--703",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press",
number = "3",
}