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An unexpected link between angiotensinogen and thrombin
Author(s) -
Wang Yunjie,
Ragg Hermann
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.06.021
Subject(s) - thrombin , lamprey , chemistry , antagonist , medicine , endocrinology , hormone , biology , biochemistry , receptor , platelet , fishery
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 × 10 4 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.