1x2w
From Proteopedia
Crystal Structure of Apo-Habu IX-bp at pH 4.6
Structural highlights
Function[SLA_PROFL] Anticoagulant protein which binds to the gamma-carboxyglutamic acid-domain regions of factor IX (F9) (but not factor X) in the presence of calcium with a 1 to 1 stoichiometry.[1] [2] [IXXB_PROFL] 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.[3] [4] [5] 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.[6] [7] [8] 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 PubMedCoagulation factor IX-binding protein, isolated from Trimeresurus flavoviridis (IX-bp), is a C-type lectin-like protein. It is an anticoagulant consisting of homologous subunits, A and B. Each subunit has a Ca(2+)-binding site with a unique affinity (K(d) values of 14muM and 130muM at pH 7.5). These binding characteristics are pH-dependent and, under acidic conditions, the Ca(2+) binding of the low-affinity site was reduced considerably. In order to identify which site has high affinity and to investigate the pH-dependent Ca(2+) release mechanism, we have determined the crystal structures of IX-bp at pH 6.5 and pH 4.6 (apo form), and compared the Ca(2+)-binding sites with each other and with those of the solved structures under alkaline conditions; pH 7.8 and pH 8.0 (complexed form). At pH 6.5, Glu43 in the Ca(2+)-binding site of subunit A displayed two conformations. One (minor) is that in the alkaline state, and the other (major) is that at pH 4.6. However, the corresponding Gln43 residue of subunit B is in only a single conformation, which is almost identical with that in the alkaline state. At pH 4.6, Glu43 of subunit A adopts a conformation similar to that of the major conformer observed at pH 6.5, while Gln43 of subunit B assumes a new conformation, and both Ca(2+) positions are occupied by water molecules. These results showed that Glu43 of subunit A is much more sensitive to protonation than Gln43 of subunit B, and the conformational change of Glu43 occurs around pH6.5, which may correspond to the step of Ca(2+) release. pH-Dependent structural changes at Ca(2+)-binding sites of coagulation factor IX-binding protein.,Suzuki N, Fujimoto Z, Morita T, Fukamizu A, Mizuno H J Mol Biol. 2005 Oct 14;353(1):80-7. PMID:16165155[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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