Contribution of the N-terminal and C-terminal domains of haemaphysalin to inhibition of activation of plasma kallikrein-kinin system.
Haemaphysalin is a kallikrein-kinin system inhibitor from hard tick Haemaphysalis longicornis, and consists of two Kunitz type protease inhibitor domains. Each domain as well as haemaphysalin inhibited intrinsic coagulation by inhibiting activation of the kallikrein-kinin system without affecting the amidolytic activities of intrinsic coagulation factors, indicating that both domains were involved in the inhibition through a similar mechanism to that for haemaphysalin. Reconstitution experiments showed that the C-terminal domain contributed more predominantly to this inhibition. Direct binding assaying showed that the C-terminal domain could bind to the cell-binding region of high molecular weight kininogen (HK), suggesting that it also binds to the cell-binding region of factor XII. Judging from these findings, the C-terminal domain may more effectively inhibit the association of factor XII and HK with the cell surface by binding to cell-binding regions, and hence would predominantly contribute to the inhibition of activation of the kallikrein-kinin system.
Kato
Noriko
N
Laboratory of Chemistry and Utilization of Animal Resources, Faculty of Agriculture, Kobe University, Kobe, Hyogo 657-8501, Japan.
Okayama
Takahide
T
Isawa
Haruhiko
H
Yuda
Masao
M
Chinzei
Yasuo
Y
Iwanaga
Shiroh
S
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005174:Factor XII / Q000378:metabolism; D015956:Factor XIIa / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D026863:Ixodidae; D016234:Kallikrein-Kinin System / Q000502:physiology*; D007704:Kininogens / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011288:Prekallikrein / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D005353:Fibronectins; D007704:Kininogens; D010455:Peptides; D011994:Recombinant Proteins; C502360:haemaphysalin protein, Haemaphysalis longicornis; D005174:Factor XII; D011288:Prekallikrein; D015956:Factor XIIa; D013917:Thrombin