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SpeB–Spi: a novel protease–inhibitor pair from Streptococcus pyogenes
Author(s) -
Kagawa Todd F.,
O'Toole Paul W.,
Cooney Jakki C.
Publication year - 2005
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2005.04708.x
Subject(s) - streptococcus pyogenes , protease , proteases , cysteine protease , biology , biochemistry , protease inhibitor (pharmacology) , protein precursor , microbiology and biotechnology , gene , enzyme , genetics , bacteria , virus , antiretroviral therapy , viral load , staphylococcus aureus
Summary This study presents evidence for a novel protease–protease inhibitor couple, SpeB–Spi, in the human pathogen Streptococcus pyogenes . The gene for the inhibitor Spi is located directly downstream of the gene for the streptococcal cysteine protease SpeB. Spi is 37% identical and 70% similar to the sequence of the SpeB propeptide, suggesting that Spi and the SpeB propeptide might bind to SpeB in an analogous manner. Secondary structure predictions and molecular modelling suggested that Spi would adopt a structure similar to the SpeB propeptide. The spi gene was co‐transcribed with speB on the 1.7 knt and 2.2 knt transcripts previously identified for speB . The Spi protein was purified by SpeB‐affinity chromatography from the S. pyogenes cytoplasm. Recombinant Spi was produced and purified, and shown to bind to SpeB and to inhibit its protease activity. Although a similar genetic arrangement of protease and inhibitor is present in staphylococci, this is the first example of an inhibitor molecule that is a structural homologue of the cognate propeptide, and which is genetically linked to the protease gene. Thus, this represents a novel system whereby bacteria may control the intracellular activity of their proteases.