title: Purification of factor XIa inhibitor from human platelets.
abstract: An inhibitor of activated factor XI (FXIa) in human platelets was recently identified as an amyloid beta-protein precursor (APP). We purified an FXIa inhibitor (XIaI) from the supernatant of activated human platelets, and assessed its inhibitor activity toward FXIa amidolytic activity. Approximately 90 micrograms of XIaI that cross-reacted with anti-APP antibody was obtained from two hundred units of platelet suspension by employing a six-step column chromatography procedure. The molecular weight of the purified XIaI was 94,000. The Ki value of XIaI to factor XIa was 526 +/- 120 pM, and the inhibition was enhanced by the addition of ZnCl2. The amino-terminal sequence of XIaI was L-E-V-P-T-D-G-N-A-, which is identical to that for the leucine (N18) to alanine (N26) sequence of APP751 and the amino-terminal sequence of protease nexin-2.
authors.affiliation: Department of Clinico-laboratory Medicine, Kansai Medical University, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Komiyama
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: H
authors.initials: H
authors.lastname: Egawa
authors.forename: S
authors.initials: S
authors.lastname: Okubo
authors.forename: K
authors.initials: K
authors.lastname: Yasunaga
authors.forename: K
authors.initials: K
authors.lastname: Murata
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000302:isolation & purification* / Q000494:pharmacology; D001777:Blood Coagulation; D001792:Blood Platelets / Q000737:chemistry*; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D002863:Chromogenic Compounds; D004591:Electrophoresis, Polyacrylamide Gel; D015945:Factor XIa / Q000037:antagonists & inhibitors*; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D017385:Sequence Homology; D015842:Serine Proteinase Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D016564:Amyloid beta-Protein Precursor; D002863:Chromogenic Compounds; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; C040190:S 2366; D015945:Factor XIa; D011761:Pyrrolidonecarboxylic Acid