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- Title
An unexpected link between angiotensinogen and thrombin
- Authors
Wang, Yunjie; Ragg, Hermann
- Abstract
Abstract: Angiotensinogen is well known as source protein for a group of potent vasoactive hormones, however, a discrete biochemical activity of the angiotensinogen body is not known. Here we investigated angiotensinogen from the lamprey Lampetra fluviatilis (L. fluviatilis), an early-diverged vertebrate. The recombinantly produced protein showed progressive inhibitory activity towards human α-thrombin with a second-order rate constant of 2.6×104 M−1 min−1. Heparin enhanced the reaction rate >800-fold with a bell-shaped dose-response curve and a stoichiometry of inhibition (SI) of 1.3, revealing lamprey angiotensinogen as an effective α-thrombin inhibitor. Genomic, biochemical, and protein sequence data indicate that angiotensinogen and heparin cofactor II (HCII) originated from a common ancestral thrombin antagonist, thus providing insight into an early stage of thrombin control.
- Subjects
ANGIOTENSINS; THROMBIN; ANTITHROMBIN III; SERPINS; BLOOD coagulation; HORMONES; BIOCHEMISTRY; LAMPREYS
- Publication
FEBS Letters, 2011, Vol 585, Issue 14, p2395
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2011.06.021