Human thrombin variable region 1, including E39, is involved in interactions with alpha 1-antitrypsin M358R and protein C.
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.
Gaussem
P
P
INSERM U.428, UFR des Sciences Pharmaceutiques et Biologiques, Université Paris V, France.
Picard
V
V
Chadeuf
G
G
Arnaud
E
E
Aiach
M
M
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*
D006629:Hirudins; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011486:Protein C; D000515:alpha 1-Antitrypsin; D013917:Thrombin