Structural highlights
Function
[IXB_TRIFL] When linked to subunit A of IX/X-bp, anticoagulant protein which binds to the gamma-carboxyglutamic acid-domain regions of factors IX (F9) and factor X (10) in the presence of calcium with a 1 to 1 stoichiometry.[1] [2] [3] When linked to subunit A of IX-bp, anticoagulant protein which binds to the gamma-carboxyglutamic acid-domain regions of factor IX (but not to factor X) in the presence of calcium with a 1 to 1 stoichiometry.[4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Coagulation factor IX-binding protein (IX-bp) isolated from the venom of the habu snake (Trimeresurus flavoviridis) is a disulfide-linked heterodimer consisting of homologous subunits A and B. The structure of IX-bp has been solved by X-ray crystallography at 2.6 A resolution to a crystallographic R -value of 0.181. The main-chain fold of each subunit is homologous to the carbohydrate-recognition domain of C-type lectins (C-type CRDs) except for the extended central loop. The structure is almost identical with that of factors IX and X-binding protein (IX/X-bp) as expected from the high level of amino acid sequence homology. The functional difference in ligand recognition from IX/X-bp must reside in the amino acid differences. A continuity of different amino acid residues located from the C-terminal of the second alpha-helix to the following loop forms the local conformational difference in this region between the two proteins. This loop participates in the formation of the concave surface between the two subunits, the putative binding site for the Gla-domain (gamma-carboxyglutamic acid-containing domain) of the coagulation factors. Another difference between the two proteins is in the relative disposition of subunits A and B. When the B subunits are superimposed, about a 6 degrees rotation is required for the superposition of the A subunits. A calcium ion links the second alpha-helix region to the C-terminal tail in each subunit and helps to stabilize the structure for Gla-domain binding. The interface created by the central loop swapping in the dimer IX-bp is almost identical with that seen within the monomeric C-type CRDs. This dimer forms as the result of the amino acid deletion in the linker region of the central loop of the original C-type lectins. Such a dimerization disrupts the lectin active site and creates a Gla-domain binding site, imparting functional diversity.
Crystal structure of coagulation factor IX-binding protein from habu snake venom at 2.6 A: implication of central loop swapping based on deletion in the linker region.,Mizuno H, Fujimoto Z, Koizumi M, Kano H, Atoda H, Morita T J Mol Biol. 1999 May 28;289(1):103-12. PMID:10339409[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Atoda H, Morita T. A novel blood coagulation factor IX/factor X-binding protein with anticoagulant activity from the venom of Trimeresurus flavoviridis (Habu snake): isolation and characterization. J Biochem. 1989 Nov;106(5):808-13. PMID:2613688
- ↑ Atoda H, Yoshida N, Ishikawa M, Morita T. Binding properties of the coagulation factor IX/factor X-binding protein isolated from the venom of Trimeresurus flavoviridis. Eur J Biochem. 1994 Sep 1;224(2):703-8. PMID:7925387
- ↑ Atoda H, Ishikawa M, Yoshihara E, Sekiya F, Morita T. Blood coagulation factor IX-binding protein from the venom of Trimeresurus flavoviridis: purification and characterization. J Biochem. 1995 Nov;118(5):965-73. PMID:8749314
- ↑ Atoda H, Morita T. A novel blood coagulation factor IX/factor X-binding protein with anticoagulant activity from the venom of Trimeresurus flavoviridis (Habu snake): isolation and characterization. J Biochem. 1989 Nov;106(5):808-13. PMID:2613688
- ↑ Atoda H, Yoshida N, Ishikawa M, Morita T. Binding properties of the coagulation factor IX/factor X-binding protein isolated from the venom of Trimeresurus flavoviridis. Eur J Biochem. 1994 Sep 1;224(2):703-8. PMID:7925387
- ↑ Atoda H, Ishikawa M, Yoshihara E, Sekiya F, Morita T. Blood coagulation factor IX-binding protein from the venom of Trimeresurus flavoviridis: purification and characterization. J Biochem. 1995 Nov;118(5):965-73. PMID:8749314
- ↑ Mizuno H, Fujimoto Z, Koizumi M, Kano H, Atoda H, Morita T. Crystal structure of coagulation factor IX-binding protein from habu snake venom at 2.6 A: implication of central loop swapping based on deletion in the linker region. J Mol Biol. 1999 May 28;289(1):103-12. PMID:10339409 doi:http://dx.doi.org/10.1006/jmbi.1999.2756
