Oligopeptidase B: A processing peptidase involved in pathogenesis

Abstract

Oligopeptidase B is a “processing peptidase” from the prolyl oligopeptidase family of serine peptidases present in Gram negative bacteria, protozoa and plants. Unlike the prototype prolyl oligopeptidase, oligopeptidase B hydrolyses peptides on the carboxyl side of pairs of basic amino acid residues. Molecular modelling and mutation studies have identified carboxyl dyads in the C-terminal catalytic domain that mediate substrate and inhibitor binding. The peptidase is efficiently inhibited by non-peptide irreversible serine peptidase inhibitors, peptidyl-chloromethylketones, -phosphonate α-aminoalkyl diphenyl esters with basic residues at P1, and tripeptide aldehydes, but not by proteinaceous host plasma inhibitors such as α 2-macroglobulin and serpins. Access of these large molecular mass inhibitors and substrates larger than ∼30 amino acid residues to the catalytic cleft is restricted by the N-terminal β-propeller domain. The physiological role of oligopeptidase B from various sources has not yet been elucidated. However, the peptidase has been identified as an important virulence factor and therapeutic agent in animal trypanosomosis. This review highlights the structure–function properties of oligopeptidase B in context with its physiological and/or pathological roles which make the enzyme a promising drug target.