title: Snake-venom-derived Factor IX-binding protein specifically blocks the gamma-carboxyglutamic acid-rich-domain-mediated membrane binding of human Factors IX and X.
abstract: A potent anticoagulant protein, IX-bp (Factor IX binding protein), has been isolated from the venom of Trimeresurus flavoviridis (habu snake) and is known to bind specifically to the Gla (gamma-carboxyglutamic acid-rich) domain of Factor IX. To evaluate the molecular basis for its anticoagulation activity, we assessed its interactions with various clotting factors. We found that the anticoagulation activity is primarily due to binding to the Gla domains of Factors IX and X, thus preventing these factors from recognizing phosphatidylserine on the plasma membrane. The present study suggests that ligands that bind to the Gla domains of Factors IX and X may have the potential to become novel anticoagulants.
authors.affiliation: Functional Nucleic Acids Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba City 305-8566, Ibaraki, Japan.
authors.forename: Subash C B
authors.initials: SC
authors.lastname: Gopinath
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shikamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizuno
authors.forename: Penmetcha K R
authors.initials: PK
authors.lastname: Kumar
mesh_terms: D015055:1-Carboxyglutamic Acid / Q000737:chemistry; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000502:physiology; D003435:Crotalid Venoms / Q000494:pharmacology*; D005164:Factor IX / Q000378:metabolism*; D005170:Factor X / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D017434:Protein Structure, Tertiary; D030162:Reptilian Proteins / Q000494:pharmacology*; D020349:Surface Plasmon Resonance; D017841:Trimeresurus
chemical_list: D000925:Anticoagulants; D003435:Crotalid Venoms; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010718:Phosphatidylserines; D030162:Reptilian Proteins; C070302:factor IX-factor X-binding protein, Crotalinae; D015055:1-Carboxyglutamic Acid; D005164:Factor IX; D005170:Factor X