Identification and characterization of the plasma kallikrein-kinin system inhibitor, haemaphysalin, from hard tick, Haemaphysalis longicornis.
The plasma kallikrein-kinin system inhibitor, haemaphysalin, from the hard tick, Haemaphysalis longicornis, was identified. It was found that haemaphysalin inhibited activation of the plasma kallikrein-kinin system by interfering with reciprocal activation between factor XII and prekallikrein. It did not, however, inhibit amidolytic activities of factor XIIa and kallikrein. Direct binding assay indicated that factor XII/XIIa and high molecular weight kininogen (HK) are the target molecules of haemaphysalin, and that Zn2+ ions are involved in the interactions of haemaphysalin with these target molecules. This suggests that haemaphysalin interacts with target molecules by recognizing their conformational changes induced by Zn2+ ions. Furthermore, haemaphysalin interacted with the fibronectin type II domain and domain D5, the cell binding domains of factor XII and HK, respectively. This finding suggests that haemaphysalin interferes with the association of factor XII and the prekallikrein-HK complex with a biologic activating surface by binding to these cell-binding domains, leading to inhibition of the reciprocal activation between factor XII and prekallikrein.
Kato
Noriko
N
Laboratory of Chemistry and Utilization of Animal Resources, Faculty of Agriculture, Kobe University, Kobe, Japan.
Iwanaga
Shiroh
S
Okayama
Takahide
T
Isawa
Haruhiko
H
Yuda
Masao
M
Chinzei
Yasuo
Y
D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000494:pharmacology*; D005174:Factor XII / Q000037:antagonists & inhibitors / Q000378:metabolism; D015956:Factor XIIa / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D016234:Kallikrein-Kinin System / Q000187:drug effects*; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000378:metabolism; D019679:Kininogen, High-Molecular-Weight / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D012469:Salivary Glands / Q000737:chemistry; D013987:Ticks / Q000737:chemistry*; D015032:Zinc / Q000378:metabolism
D002352:Carrier Proteins; D019679:Kininogen, High-Molecular-Weight; C502360:haemaphysalin protein, Haemaphysalis longicornis; D005174:Factor XII; D007610:Kallikreins; D015956:Factor XIIa; D015032:Zinc