Structural highlights
Publication Abstract from PubMed
Cysteine protease SpeB is secreted from Streptococcus pyogenes and has been studied as a potential virulence factor since its identification almost 70 years ago. Here, we report the crystal structures of apo mature SpeB to 1.06 Angstrom resolution as well as complexes with the general cysteine protease inhibitor E64 and a novel substrate mimetic peptide inhibitor. These structures uncover conformational changes associated with maturation of SpeB from the inactive zymogen to its active form and identify the residues required for substrate binding. With the use of a newly developed fluorogenic tri-peptide substrate to measure SpeB activity, we determined IC50 values for E64 and our new peptide inhibitor and the effects of mutations within the C-terminal, active-site loop. The structures and mutational analysis suggest conformational movements of the glycine-rich C-terminal loop are important for the recognition and recruitment of biological substrates and release of hydrolyzed products.
Ultra-high and high resolution structures and mutational analysis of monomeric Streptococcus pyogenes SpeB reveal a functional role for the glycine-rich C-terminal loop.,Gonzalez-Paez GE, Wolan DW J Biol Chem. 2012 May 29. PMID:22645124[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gonzalez-Paez GE, Wolan DW. Ultra-high and high resolution structures and mutational analysis of monomeric Streptococcus pyogenes SpeB reveal a functional role for the glycine-rich C-terminal loop. J Biol Chem. 2012 May 29. PMID:22645124 doi:10.1074/jbc.M112.361576
