2UZJ

Crystal structure of the mature streptococcal cysteine protease, mSpeB

Summary for 2UZJ

• Entry DOI: 10.2210/pdb2uzj/pdb
• Descriptor: STREPTOPAIN, N-[N-[1-HYDROXYCARBOXYETHYL-CARBONYL]LEUCYLAMINO-BUTYL]-GUANIDINE (3 entities in total)
• Functional Keywords: proteinase, papain family, cysteine protease, hydrolase, dimer, clan ca, exotoxin, family 10, peptidase
• Biological source: STREPTOCOCCUS PYOGENES
• Cellular location: Secreted: Q5X9P3
• Total number of polymer chains: 2
• Total formula weight: 55943.92

Authors

Olsen, J.G.,Dagil, R.,Niclasen, L.M.,Soerensen, O.E.,Kragelund, B.B. (deposition date: 2008-09-16, release date: 2009-09-08, Last modification date: 2024-10-09)

Primary citation

Olsen, J.G.,Dagil, R.,Niclasen, L.M.,Soerensen, O.E.,Kragelund, B.B.
Structure of the Mature Streptococcal Cysteine Protease Exotoxin Mspeb in its Active Dimeric Form.
J.Mol.Biol., 393:693-, 2009

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.

PubMed: 19712682
DOI: 10.1016/J.JMB.2009.08.046

Experimental method

X-RAY DIFFRACTION (1.55 Å)