title: Human thrombin variable region 1, including E39, is involved in interactions with alpha 1-antitrypsin M358R and protein C.
abstract: We used an antithrombin autoantibody (IgG D), the epitope of which encompasses ABE1 and amino acids located within variable region 1, to study thrombin interactions with R358 alpha 1-AT and protein C. IgG D inhibited the thrombin interaction with R358 alpha 1-AT, while hirugen had no effect, indicating that the interaction of R358 alpha 1-AT with thrombin may involve the VR1 subsite. We also obtained evidence that VR1 may be involved in the activation of protein C by thrombin in the absence of thrombomodulin. Moreover, IgG D attenuated the inhibitory effect of calcium ions during protein C activation by thrombin, probably by masking E39 within the VR1 site.
authors.affiliation: INSERM U.428, UFR des Sciences Pharmaceutiques et Biologiques, Université Paris V, France.
authors.forename: P
authors.initials: P
authors.lastname: Gaussem
authors.forename: V
authors.initials: V
authors.lastname: Picard
authors.forename: G
authors.initials: G
authors.lastname: Chadeuf
authors.forename: E
authors.initials: E
authors.lastname: Arnaud
authors.forename: M
authors.initials: M
authors.lastname: Aiach
mesh_terms: D000595:Amino Acid Sequence; D014644:Genetic Variation; D006629:Hirudins / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D017354:Point Mutation; D011486:Protein C / Q000378:metabolism*; D013379:Substrate Specificity; D013917:Thrombin / Q000235:genetics* / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
chemical_list: D006629:Hirudins; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011486:Protein C; D000515:alpha 1-Antitrypsin; D013917:Thrombin