Variegin, a novel class of fast and tight binding thrombin inhibitor from the tropical bont tick
Koh, Cho Yeow; Kazimirova, Maria; Trimnell, Adama; Takac, Peter; Labuda, Milan; Nuttall, Patricia A.; Kini, R. Manjunatha. 2007 Variegin, a novel class of fast and tight binding thrombin inhibitor from the tropical bont tick. Journal of Biological Chemistry, 282 (40). 29101-29143. 10.1074/jbc.M705600200Full text not available from this repository.
Tick saliva contains potent antihemostatic molecules that help ticks obtain their enormous blood meal during prolonged feeding. We isolated thrombin inhibitors present in the salivary gland extract from partially fed female Amblyomma variegatum, the tropical bont tick, and characterized the most potent, variegin, one of the smallest (32 residues) thrombin inhibitors found in nature. Full-length variegin and two truncated variants were chemically synthesized. Despite its small size and flexible structure, variegin binds thrombin with strong affinity (Ki 10.4 pM) and high specificity. Results using the truncated variants indicated that the seven residues at the N terminus affected the binding kinetics; when removed, the binding characteristics changed from fast to slow. Further, the thrombin active site binding moiety of variegin is in the region of residues 8–14, and the exosite-I binding moiety is within residues 15–32. Our results show that variegin is structurally and functionally similar to the rationally designed thrombin inhibitor, hirulog. However, compared with hirulog, variegin is a more potent inhibitor, and its inhibitory activity is largely retained after cleavage by thrombin.
|Programmes:||CEH Programmes pre-2009 publications > Biodiversity|
|Additional Keywords:||tick saliva, thrombin inhibitors, Amblyomma variegatum|
|NORA Subject Terms:||Biology and Microbiology|
|Date made live:||28 Nov 2007 10:06|
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