Protamine: a unique and potent inhibitor of oligopeptidase B.
Oligopeptidase B is a serine endopeptidase found in prokaryotes, unicellular eukaryotes and higher plants. The enzyme has been shown recently to play a central role in the pathogenesis of several parasitic diseases such as African trypanosomiasis, and to be a potential therapeutic target. This study reports that protamine, a basic peptide rich in arginine, is a potent inhibitor at the nanomolar level of oligopeptidase B from E. coli and wheat. Protamines 1B, 2C, 3A and TP17 displayed similar inhibitory activities and were capable of binding strongly to oligopeptidase B without proteolytic cleavage. The concentration of protamine needed for 50% inhibition (IC50) of oligopeptidase B was 10(4)-fold lower than the IC50 of trypsin. Oligopeptidase B was highly sensitive to inhibition by protamines even in the presence of serum (IC50, 1 microM). These data indicate that protamines might provide information useful for the design of more specific synthetic oligopeptidase B inhibitors.
Tsuji
Akihiko
A
Department of Biological Science and Technology, The faculty of Engineering, The University of Tokushima, 2-1 Minamijosanjima, Tokushima 770-8506, Japan. tsuji@bio.tokushima-u.ac.jp
Yoshimoto
Tadashi
T
Yuasa
Keizo
K
Matsuda
Yoshiko
Y
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D011479:Protamines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014908:Triticum / Q000201:enzymology
D004791:Enzyme Inhibitors; D011479:Protamines; D012697:Serine Endopeptidases; C090703:oligopeptidase B