The C-terminal binding domain of hirullin P18. Antithrombin activity and comparison to hirudin peptides.
Hirullin P18 is a 61-amino acid hirudin-related protein having potent antithrombin activity. Similar to hirudin, it contains a highly acidic C-terminus, but has a significantly different sequence from any other known hirudin variant. The present study demonstrates that the C-terminal fragment acetyl-hirullin P18(41-62) [corrected] possesses an antithrombin potency similar to that of acetyl-desulfatohirudin(45-65). Additionally, like the hirudin fragment analog, it inhibits fibrin-clot formation by binding to a non-catalytic site on thrombin. Sequential shortening of the hirullin P18 C-terminal fragment demonstrates the critical nature of Phe51, which corresponds to the important Phe56 residue of hirudin. Although the sequences of hirullin P18(54-61) and hirudin(59-65) have substantial differences, the C-terminal functional domain represented by hirullin P18(50-61) appears to be comparable to hirudin(55-65) in terms of its functional role in antithrombin activity.
Merrell Dow Research Institute, Cincinnati, Ohio 45215.
J L
JL
Krstenansky
T J
TJ
Owen
M T
MT
Yates
S J
SJ
Mao
D000595:Amino Acid Sequence; D006629:Hirudins / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*
D006629:Hirudins; D010455:Peptides; C065797:hirullin P18; D013917:Thrombin