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PDBsum entry 1j34
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protein metals Protein-protein interface(s) links
Protein binding/blood clotting PDB id
1j34

 

 

 

 

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Contents
Protein chains
129 a.a. *
123 a.a. *
46 a.a. *
Metals
_CA ×7
_MG ×3
Waters ×444
* Residue conservation analysis
PDB id:
1j34
Name: Protein binding/blood clotting
Title: Crystal structure of mg(ii)-and ca(ii)-bound gla domain of factor ix complexed with binding protein
Structure: Coagulation factor ix-binding protein a chain. Chain: a. Synonym: coagulation factor ix binding protein chain a. Coagulation factor ix-binding protein b chain. Chain: b. Coagulation factor ix. Chain: c. Fragment: gla domain. Ec: 3.4.21.22
Source: Trimeresurus flavoviridis. Organism_taxid: 88087. Secretion: venom. Bos taurus. Cattle. Organism_taxid: 9913. Secretion: plasma
Biol. unit: Trimer (from PQS)
Resolution:
1.55Å     R-factor:   0.183     R-free:   0.212
Authors: Y.Shikamoto,T.Morita,Z.Fujimoto,H.Mizuno
Key ref:
Y.Shikamoto et al. (2003). Crystal structure of Mg2+- and Ca2+-bound Gla domain of factor IX complexed with binding protein. J Biol Chem, 278, 24090-24094. PubMed id: 12695512 DOI: 10.1074/jbc.M300650200
Date:
20-Jan-03     Release date:   08-Jul-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q7LZ71  (SLA_PROFL) -  Snaclec coagulation factor IX-binding protein subunit A from Protobothrops flavoviridis
Seq:
Struc: 		129 a.a.
129 a.a.
Protein chain
Pfam   ArchSchema ?
P23807  (SL9B_PROFL) -  Snaclec coagulation factor IX/factor X-binding protein subunit B from Protobothrops flavoviridis
Seq:
Struc: 		146 a.a.
123 a.a.
Protein chain
Pfam   ArchSchema ?
P00741  (FA9_BOVIN) -  Coagulation factor IX from Bos taurus
Seq:
Struc: 		462 a.a.
46 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 12 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain C: E.C.3.4.21.22  - coagulation factor IXa.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolyzes one Arg-|-Ile bond in factor X to form factor Xa.

 

 
DOI no: 10.1074/jbc.M300650200 J Biol Chem 278:24090-24094 (2003)
PubMed id: 12695512  
 
 
Crystal structure of Mg2+- and Ca2+-bound Gla domain of factor IX complexed with binding protein.
Y.Shikamoto, T.Morita, Z.Fujimoto, H.Mizuno.
 
  ABSTRACT  
 
Factor IX is an indispensable protein required in the blood coagulation cascade. It binds to the surface of phospholipid membrane by means of a gamma-carboxyglutamic acid (Gla) domain situated at the N terminus. Recently, we showed that physiological concentrations of Mg2+ ions affect the native conformation of the Gla domain and in doing so augment the biological activity of factor IXa and binding affinity with its binding protein even in the presence of Ca2+ ions. Here we report on the crystal structures of the Mg2+/Ca2+-bound and Ca2+-bound (Mg2+-free) factor IX Gla domain (IXGD1-46) in complex with its binding protein (IX-bp) at 1.55 and 1.80 A resolutions, respectively. Three Mg2+ and five Ca2+ ions were bound in the Mg2+/Ca2+-bound IXGD1-46, and the Mg2+ ions were replaced by Ca2+ ions in Mg2+-free IXGD1-46. Comparison of Mg2+/Ca2+-bound with Ca2+-bound structures of the complexes showed that Mg2+ ion, which formed a bridge between IXGD1-46 and IX-bp, forced IXGD1-46 to rotate 4 degrees relative to IX-bp and hence might be the cause of a more tight interaction between the molecules than in the case of the Mg2+-free structure. The results clearly suggest that Mg2+ ions are required to maintain native conformation and in vivo function of factor IX Gla domain during blood coagulation.
 
  Selected figure(s)  
 
Figure 1.
FIG. 1. Stereo view of overall structure of the GD1-46/IX-bp complex. Ribbon model viewed perpendicular to the pseudodyad of the molecule. The subunits A and B of IX-bp are magenta and green. IXGD1-46 is in white, and the interchain disulfide bond is shown in yellow. The bound Mg2^+ and Ca^2^+ ions are drawn as orange and blue spheres, respectively. 		Figure 5.
FIG. 5. Model of factor IXa. The epidermal growth factor (green) and serine protease (yellow) domains of factor IXa (42) are shown connected to the IXGD1-46 structure (white), using factor VIIa structure (17) as a reference model. The bound Mg2^+ and Ca^2^+ ions are drawn as orange and blue spheres, respectively. D-Phe-Pro-Arg-chloromethylketone, which is bound to the active site, is shown as a red stick model. The phospholipid membrane surface is shown by a yellow line. Hydrophobic residues (yellow), basic residues (purple) and Mg2^+ ion (Mg-1) of GD1-46 are possible candidates for membrane binding.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 24090-24094) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21197556 D.Shen, X.Xu, H.Wu, L.Peng, Y.Zhang, J.Song, and Q.Su (2011).
Metal ion binding to anticoagulation factor II from the venom of Agkistrodon acutus: stabilization of the structure and regulation of the binding affinity to activated coagulation factor X.
  J Biol Inorg Chem, 16, 523-537.  
20830601 H.Wu, X.Xu, D.Shen, L.Peng, J.Song, and Y.Zhang (2011).
Binding of Ca2+ and Zn2+ to factor IX/X-binding protein from venom of Agkistrodon halys Pallas: stabilization of the structure during GdnHCl-induced and thermally induced denaturation.
  J Biol Inorg Chem, 16, 69-79.  
21277886 T.Sajevic, A.Leonardi, and I.Križaj (2011).
Haemostatically active proteins in snake venoms.
  Toxicon, 57, 627-645.  
20419068 B.de Courcy, L.G.Pedersen, O.Parisel, N.Gresh, B.Silvi, J.Pilmé, and J.P.Piquemal (2010).
Understanding selectivity of hard and soft metal cations within biological systems using the subvalence concept. I. Application to blood coagulation: direct cation-protein electronic effects vs. indirect interactions through water networks.
  J Chem Theory Comput, 6, 1048-1063.  
  20180816 Y.Z.Ohkubo, J.H.Morrissey, and E.Tajkhorshid (2010).
Dynamical view of membrane binding and complex formation of human factor VIIa and tissue factor.
  J Thromb Haemost, 8, 1044-1053.  
19817987 A.S.Messer, W.H.Velander, and S.P.Bajaj (2009).
Contribution of magnesium in binding of factor IXa to the phospholipid surface: implications for vitamin K-dependent coagulation proteins.
  J Thromb Haemost, 7, 2151-2153.  
19279192 D.Fujisawa, Y.Yamazaki, and T.Morita (2009).
Re-evaluation of M-LAO, L-amino acid oxidase, from the venom of Gloydius blomhoffi as an anticoagulant protein.
  J Biochem, 146, 43-49.  
18977769 M.Ishikawa, M.Kumashiro, Y.Yamazaki, H.Atoda, and T.Morita (2009).
Anticoagulant Mechanism of Factor IX/factor X-binding Protein Isolated from the Venom of Trimeresurus flavoviridis.
  J Biochem, 145, 123-128.  
19244162 M.J.Heeb, D.Prashun, J.H.Griffin, and B.N.Bouma (2009).
Plasma protein S contains zinc essential for efficient activated protein C-independent anticoagulant activity and binding to factor Xa, but not for efficient binding to tissue factor pathway inhibitor.
  FASEB J, 23, 2244-2253.  
19495561 R.Doley, and R.M.Kini (2009).
Protein complexes in snake venom.
  Cell Mol Life Sci, 66, 2851-2871.  
19500239 S.Agah, and S.P.Bajaj (2009).
Role of magnesium in factor XIa catalyzed activation of factor IX: calcium binding to factor IX under physiologic magnesium.
  J Thromb Haemost, 7, 1426-1428.  
19361276 T.Zögg, and H.Brandstetter (2009).
Activation mechanisms of coagulation factor IX.
  Biol Chem, 390, 391-400.  
19184130 X.Xu, L.Zhang, D.Shen, H.Wu, L.Peng, and J.Li (2009).
Effect of metal ion substitutions in anticoagulation factor I from the venom of Agkistrodon acutus on the binding of activated coagulation factor X and on structural stability.
  J Biol Inorg Chem, 14, 559-571.  
18184865 A.Venceslá, M.A.Corral-Rodríguez, M.Baena, M.Cornet, M.Domènech, M.Baiget, P.Fuentes-Prior, and E.F.Tizzano (2008).
Identification of 31 novel mutations in the F8 gene in Spanish hemophilia A patients: structural analysis of 20 missense mutations suggests new intermolecular binding sites.
  Blood, 111, 3468-3478.  
18359797 J.Diao, and E.Tajkhorshid (2008).
Indirect role of Ca2+ in the assembly of extracellular matrix proteins.
  Biophys J, 95, 120-127.  
18540896 S.Mukherjee, A.Saha, P.Biswas, C.Mandal, and K.Ray (2008).
Structural analysis of factor IX protein variants to predict functional aberration causing haemophilia B.
  Haemophilia, 14, 1076-1081.  
17723139 E.Persson, and A.Ostergaard (2007).
Mg(2+) binding to the Gla domain of factor X influences the interaction with tissue factor.
  J Thromb Haemost, 5, 1977-1978.  
17131117 O.Taboureau, and O.H.Olsen (2007).
Computational study of coagulation factor VIIa's affinity for phospholipid membranes.
  Eur Biophys J, 36, 133-144.  
16206329 A.Bazaa, N.Marrakchi, M.El Ayeb, L.Sanz, and J.J.Calvete (2005).
Snake venomics: comparative analysis of the venom proteomes of the Tunisian snakes Cerastes cerastes, Cerastes vipera and Macrovipera lebetina.
  Proteomics, 5, 4223-4235.  
  16508118 N.Suzuki, Y.Shikamoto, Z.Fujimoto, T.Morita, and H.Mizuno (2005).
Crystallization and preliminary X-ray analysis of coagulation factor IX-binding protein from habu snake venom at pH 6.5 and 4.6.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 147-149.  
16102046 Q.Lu, J.M.Clemetson, and K.J.Clemetson (2005).
Snake venoms and hemostasis.
  J Thromb Haemost, 3, 1791-1799.  
15314527 M.Schenone, B.C.Furie, and B.Furie (2004).
The blood coagulation cascade.
  Curr Opin Hematol, 11, 272-277.  
14684891 T.Batuwangala, M.Leduc, J.M.Gibbins, C.Bon, and E.Y.Jones (2004).
Structure of the snake-venom toxin convulxin.
  Acta Crystallogr D Biol Crystallogr, 60, 46-53.
PDB code: 1uos
15005338 T.Morita (2004).
Use of snake venom inhibitors in studies of the function and tertiary structure of coagulation factors.
  Int J Hematol, 79, 123-129.  
14580195 K.Horii, D.Okuda, T.Morita, and H.Mizuno (2003).
Structural characterization of EMS16, an antagonist of collagen receptor (GPIa/IIa) from the venom of Echis multisquamatus.
  Biochemistry, 42, 12497-12502.
PDB code: 1ukm
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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