title: An unexpected link between angiotensinogen and thrombin.
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 2.6×10(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.
authors: Department of Biotechnology, Faculty of Technology, Bielefeld University, Bielefeld, Germany.
authors: Yunjie
authors: Y
authors: Wang
authors: Hermann
authors: H
authors: Ragg
mesh_terms: D000595:Amino Acid Sequence; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005075:Biological Evolution; D006801:Humans; D007798:Lampreys; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013917:Thrombin / Q000235:genetics / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D000808:Angiotensinogen; D013917:Thrombin