Savignin, a potent thrombin inhibitor isolated from the salivary glands of the tick Ornithodoros savignyi (Acari: Argasidae)

被引:79
作者
Nienaber, J [1 ]
Gaspar, ARM [1 ]
Neitz, AWH [1 ]
机构
[1] Univ Pretoria, Dept Biochem, ZA-0002 Pretoria, South Africa
关键词
Ornithodoros savignyi; savignin; thrombin inhibitor; anticoagulant; ticks; ADP; adenosine diphosphate; BAPNA; N alpha-benzoyl-L-arginine p-nitroaniline;
D O I
10.1006/expr.1999.4448
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
A thrombin (E.C. 3.4.21.5) inhibitor, savignin, was isolated from the salivary glands of Ornithodoros savignyi by a combination of size exclusion, anion-exchange, and reversed-phase chromatography. The inhibitor has a molecular mass of 12,430.4 Da as deter mined by electrospray mass spectrometry. The behavior of savignin during anion-exchange chromatography indicated that it has an acidic pi. The available N-terninal sequence (residues 1-11) differed from that of ornithodorin with only one residue. Savignin inhibits thrombin-induced platelet aggregation, but has no effect on ADP- or collagen-induced aggregation. Kinetic studies indicated that savignin is a competitive, slow-, tight-binding inhibitor of alpha-thrombin (K-i = 4.89 +/- 1.39 pM). Tight-binding kinetics showed that the inhibitor has a lower affinity for gamma-thrombin (K-i = 22.3 +/- 5.9 nM). Plasmin, factor Xa, and trypsin are not inhibited by savignin. (C) 1999 Academic Press.
引用
收藏
页码:82 / 91
页数:10
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