Title: Crystal structures of Trypanosoma brucei oligopeptidase B broaden the paradigm of catalytic regulation in prolyl oligopeptidase family enzymes Canning P, Rea D, Morty RE, Fulop V Ref: PLoS ONE, 8:e79349, 2013 : PubMed
Oligopeptidase B cleaves after basic amino acids in peptides up to 30 residues. As a virulence factor in bacteria and trypanosomatid pathogens that is absent in higher eukaryotes, this is a promising drug target. Here we present ligand-free open state and inhibitor-bound closed state crystal structures of oligopeptidase B from Trypanosoma brucei, the causative agent of African sleeping sickness. These (and related) structures show the importance of structural dynamics, governed by a fine enthalpic and entropic balance, in substrate size selectivity and catalysis. Peptides over 30 residues cannot fit the enzyme cavity, preventing the complete domain closure required for a key propeller Asp/Glu to fix the catalytic His and Arg in the catalytically competent conformation. This size exclusion mechanism protects larger peptides and proteins from degradation. Similar bacterial prolyl endopeptidase and archael acylaminoacyl peptidase structures demonstrate this mechanism is conserved among oligopeptidase family enzymes across all three domains of life.
        
Representative scheme of S9N_PREPL_Peptidase_S9 structure and an image from PDBsum server
no Image
Databases
PDB-Sum
4BP9 Previously Class, Architecture, Topology and Homologous superfamily - PDB-Sum server
FSSP
4BP9Fold classification based on Structure-Structure alignment of Proteins - FSSP server