Mutations within the reactive-site region of human pancreatic secretory trypsin inhibitor confer alpha-thrombin and factor Xa inhibitory activities.
Mutations were introduced into the reactive-site region of human pancreatic secretory trypsin inhibitor (PSTI) to produce thrombin and/or factor Xa inhibitors. All of five mutants showed trypsin inhibitory activity as strong as wild-type PSTI. Moreover, the Arg (P1), Pro-Arg (P2-P1), and Pro-Arg-Ile-Tyr-Asn (P2-P1-P1'-P2'-P3') (bold letters indicated replaced amino acids compared to the wild type) mutants had additional inhibitory activities toward factor Xa, both thrombin and factor Xa, and thrombin, respectively, at 1 x 10(-5) M.
Katoh
T
T
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Tamaki
M
M
Kikuchi
N
N
Teraoka
H
H
Nagata
K
K
Yoshida
N
N
D000991:Antithrombins / Q000235:genetics / Q000494:pharmacology*; D001665:Binding Sites; D065427:Factor Xa Inhibitors; D006801:Humans; D016296:Mutagenesis; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics / Q000494:pharmacology*
D000991:Antithrombins; D065427:Factor Xa Inhibitors; D014359:Trypsin Inhibitor, Kazal Pancreatic; D013917:Thrombin