2UZJ | pdb_00002uzj

Structure of the Mature Streptococcal Cysteine Protease Exotoxin Mspeb in its Active Dimeric Form.

(2009) J Mol Biology 393: 693

• PubMed: 19712682 Search on PubMed
• DOI: https://doi.org/10.1016/j.jmb.2009.08.046
• Primary Citation of Related Structures:  
  2UZJ


• PubMed 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.

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Organizational Affiliation: 

Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, Copenhagen, Denmark.