Oligopeptidase B: a processing peptidase involved in pathogenesis.
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 alpha-aminoalkyl diphenyl esters with basic residues at P1, and tripeptide aldehydes, but not by proteinaceous host plasma inhibitors such as alpha2-macroglobulin and serpins. Access of these large molecular mass inhibitors and substrates larger than approximately 30 amino acid residues to the catalytic cleft is restricted by the N-terminal beta-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.
Coetzer
Theresa H T
TH
Biochemistry, School of Biochemistry, Genetics, Microbiology and Plant Pathology, University of KwaZulu-Natal (Pietermaritzburg campus), Private bag X01, Scottsville 3201, South Africa. coetzer@ukzn.ac.za
Goldring
J P Dean
JP
Huson
Laura E J
LE
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D013379:Substrate Specificity; D014352:Trypanosomiasis / Q000469:parasitology; D037521:Virulence Factors / Q000502:physiology
D001426:Bacterial Proteins; D010940:Plant Proteins; D015800:Protozoan Proteins; D037521:Virulence Factors; D012697:Serine Endopeptidases; C090703:oligopeptidase B