Ultrahigh and high resolution structures and mutational analysis of monomeric Streptococcus pyogenes SpeB reveal a functional role for the glycine-rich C-terminal loop.

ABSTRACT: 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 Å resolution as well as complexes with the general cysteine protease inhibitor trans-epoxysuccinyl-l-leucylamido(4-guanidino)butane 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 tripeptide substrate to measure SpeB activity, we determined IC(50) values for trans-epoxysuccinyl-l-leucylamido(4-guanidino)butane and our new peptide inhibit

SUBMITTER: Gonzalez-Paez GE 

PROVIDER: S-EPMC3397867 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature