title: Anticoagulation factor I, a snaclec (snake C-type lectin) from Agkistrodon acutus venom binds to FIX as well as FX: Ca2+ induced binding data.
abstract: Anticoagulation factor I (ACF I), a snake C-type lectin (snaclec) from the venom of Agkistrodon acutus binds specifically with activated factor X (FXa) in a Ca2+-dependent manner and prolongs the blood-clotting time in vitro. In this study, the inhibition of the coagulation pathway by ACF I was measured in vivo by activated partial thromboplastin time and prothrombin time assays and the binding of ACF I to factor IX (FIX) was investigated by native PAGE and surface plasmon resonance. The results indicate that ACF I inhibits both intrinsic and extrinsic coagulation pathways, but does not inhibit thrombin activity. ACF I also binds FIX in a Ca2+-dependent manner and their maximal binding occurs at 0.25 mM Ca2+. ACF I has a higher binding-affinity to FIX than to FX. Ca2+ is required to maintain in vivo function of FIX Gla domain for its recognition of ACF I. However, Ca2+ at high concentrations (>0.25 mM) inhibits the binding of ACF I to FIX. Ca2+ functions as a switch for the binding between ACF I and FIX. The results suggest that the binding of ACF I with FIX may play a dominant role in the anticoagulation activity of ACF I in vivo.
authors.affiliation: Department of Chemistry, University of Science and Technology of China, No. 96, Jinzhai Road, Hefei, Anhui 230026, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Xu
authors.forename: Dengke
authors.initials: D
authors.lastname: Shen
authors.forename: Jiajia
authors.initials: J
authors.lastname: Song
authors.forename: Mingchun
authors.initials: M
authors.lastname: Guo
authors.forename: Xincheng
authors.initials: X
authors.lastname: Yan
mesh_terms: D017836:Agkistrodon / Q000378:metabolism*; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003435:Crotalid Venoms / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D004586:Electrophoresis; D005164:Factor IX / Q000378:metabolism*; D015951:Factor Xa / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D011485:Protein Binding; D011517:Prothrombin Time; D013050:Spectrometry, Fluorescence; D013918:Thrombin Time
chemical_list: C031442:Agkistrodon venoms; D000925:Anticoagulants; D003435:Crotalid Venoms; D037181:Lectins, C-Type; C465285:anticoagulation factor I, Agkistrodon acutus; D005164:Factor IX; D015951:Factor Xa; D002118:Calcium