spacer
spacer
Go to PDB code: 
protein metals Protein-protein interface(s) links
Hydrolase/hydrolase inhibitor PDB id
1iod
Jmol
Contents
Protein chains
129 a.a. *
123 a.a. *
44 a.a. *
Metals
_CA ×12
Waters ×181
* Residue conservation analysis
PDB id:
1iod
Name: Hydrolase/hydrolase inhibitor
Title: Crystal structure of the complex between the coagulation factor x binding protein from snake venom and the gla domain of factor x
Structure: Coagulation factor x binding protein. Chain: a. Coagulation factor x binding protein. Chain: b. Coagulation factor x gla domain. Chain: g. Fragment: gla domain(residues 41-84). Ec: 3.4.21.6
Source: Deinagkistrodon acutus. Chinese moccasin. Organism_taxid: 36307. Bos taurus. Cattle. Organism_taxid: 9913
Biol. unit: Trimer (from PQS)
Resolution:
2.30Å     R-factor:   0.201     R-free:   0.267
Authors: H.Mizuno,Z.Fujimoto,H.Atoda,T.Morita
Key ref:
H.Mizuno et al. (2001). Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X. Proc Natl Acad Sci U S A, 98, 7230-7234. PubMed id: 11404471 DOI: 10.1073/pnas.131179698
Date:
27-Feb-01     Release date:   27-Jun-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9IAM1  (XA1_AGKAC) -  Agkisacutacin subunit A
Seq:
Struc: 		152 a.a.
129 a.a.*
Protein chain
Pfam   ArchSchema ?
Q9DEF8  (XB2_AGKAC) -  Anticoagulant protein subunit B
Seq:
Struc: 		146 a.a.
123 a.a.
Protein chain
Pfam   ArchSchema ?
P00743  (FA10_BOVIN) -  Coagulation factor X
Seq:
Struc: 		492 a.a.
44 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 13 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain G: E.C.3.4.21.6  - Coagulation factor Xa.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     blood coagulation   1 term 
  Biochemical function     binding     4 terms  

 

 
DOI no: 10.1073/pnas.131179698 Proc Natl Acad Sci U S A 98:7230-7234 (2001)
PubMed id: 11404471  
 
 
Crystal structure of an anticoagulant protein in complex with the Gla domain of factor X.
H.Mizuno, Z.Fujimoto, H.Atoda, T.Morita.
 
  ABSTRACT  
 
The gamma-carboxyglutamic acid (Gla) domain of blood coagulation factors is responsible for Ca2+-dependent phospholipid membrane binding. Factor X-binding protein (X-bp), an anticoagulant protein from snake venom, specifically binds to the Gla domain of factor X. The crystal structure of X-bp in complex with the Gla domain peptide of factor X at 2.3-A resolution showed that the anticoagulation is based on the fact that two patches of the Gla domain essential for membrane binding are buried in the complex formation. The Gla domain thus is expected to be a new target of anticoagulant drugs, and X-bp provides a basis for designing them. This structure also provides a membrane-bound model of factor X.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Overall structure of X-bp and XGD1-44 complex. (A) Stereoview of ribbon model viewed perpendicular to the pseudodyad of the molecule, showing the interface between X-bp and XGD1-44. The subunits A and B of X-bp are magenta and green. XGD1-44 is white. The side chain of Gla residues and disulfide bonds are displayed. The bound Ca^2+ ions are denoted by blue spheres. (B) Same view as in A, but molecular detail of interaction between the hydrophilic patch of XGD1-44 and positively charged X-bp, and a bridging Ca^2+. (C) Same view as in B, but between the N terminus hydrophobic patch of XGD1-44 and the C terminus of subunit B of X-bp. 		Figure 3.
Fig. 3. Model of factor Xa bound to X-bp and XGD1-44 bound to membrane. (A) Factor Xa bound to X-bp. The Gla residues are in red, bound Ca^2+ ions in blue (only labeled is Ca-8, which is identified in the present study), and disulfide bonds in green. The small molecule (dark blue) bound to the active site of the protease domain is the FX-2212a inhibitor (17). (B) Putative membrane-binding surface of XGD1-44. Same view as in A, but the scale of the figure is magnified for clarity. The hydrophobic patch includes Phe4, Leu5, and Val8, and hydrophilic patch includes Arg28, Gla25, Gla29, Gla32, and Ca-1 as a bridging Ca^2+, which are on either side of the yellow horizontal line of the putative membrane surface. Ca-X is a putative Ca^2+ ion that is taken in as another bridging Ca^2+.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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.  
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.  
18583525 A.A.Watson, J.A.Eble, and C.A.O'Callaghan (2008).
Crystal structure of rhodocytin, a ligand for the platelet-activating receptor CLEC-2.
  Protein Sci, 17, 1611-1616.
PDB code: 2vrp
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.  
18616470 H.S.Chen, J.M.Chen, C.W.Lin, K.H.Khoo, and I.H.Tsai (2008).
New insights into the functions and N-glycan structures of factor X activator from Russell's viper venom.
  FEBS J, 275, 3944-3958.  
18184585 Y.Z.Ohkubo, and E.Tajkhorshid (2008).
Distinct structural and adhesive roles of Ca2+ in membrane binding of blood coagulation factors.
  Structure, 16, 72-81.  
17456189 C.J.Lee, V.Chandrasekaran, R.E.Duke, L.Perera, and L.G.Pedersen (2007).
A proposed structural model of human protein Z.
  J Thromb Haemost, 5, 1558-1561.  
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.  
16437549 L.Autin, M.Steen, B.Dahlbäck, and B.O.Villoutreix (2006).
Proposed structural models of the prothrombinase (FXa-FVa) complex.
  Proteins, 63, 440-450.  
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.  
16336259 A.N.Zelensky, and J.E.Gready (2005).
The C-type lectin-like domain superfamily.
  FEBS J, 272, 6179-6217.  
  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.  
15502319 G.Xu, M.Teng, L.Niu, P.Liu, Y.Dong, Q.Liu, Q.Huang, and Q.Hao (2004).
Purification, characterization, crystallization and preliminary X-ray crystallographic analysis of two novel C-type lectin-like proteins: Aall-A and Aall-B from Deinagkistrodon acutus venom.
  Acta Crystallogr D Biol Crystallogr, 60, 2035-2037.  
15219196 H.C.Whinna, E.B.Lesesky, D.M.Monroe, K.A.High, P.J.Larson, and F.C.Church (2004).
Role of the gamma-carboxyglutamic acid domain of activated factor X in the presence of calcium during inhibition by antithrombin-heparin.
  J Thromb Haemost, 2, 1127-1134.  
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.  
12866057 A.N.Zelensky, and J.E.Gready (2003).
Comparative analysis of structural properties of the C-type-lectin-like domain (CTLD).
  Proteins, 52, 466-477.  
12657795 J.Zang, M.Teng, and L.Niu (2003).
Purification, crystallization and preliminary crystallographic analysis of AHP IX-bp, a zinc ion and pH-dependent coagulation factor IX binding protein from Agkistrodon halys Pallas venom.
  Acta Crystallogr D Biol Crystallogr, 59, 730-733.  
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
12923575 M.Huang, A.C.Rigby, X.Morelli, M.A.Grant, G.Huang, B.Furie, B.Seaton, and B.C.Furie (2003).
Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins.
  Nat Struct Biol, 10, 751-756.
PDB codes: 1nl1 1nl2
12834348 S.X.Wang, E.Hur, C.A.Sousa, L.Brinen, E.J.Slivka, and R.J.Fletterick (2003).
The extended interactions and Gla domain of blood coagulation factor Xa.
  Biochemistry, 42, 7959-7966.
PDB code: 1p0s
11939795 J.M.Lockett, and A.E.Mast (2002).
Contribution of regions distal to glycine-160 to the anticoagulant activity of tissue factor pathway inhibitor.
  Biochemistry, 41, 4989-4997.  
11914494 S.Liu, Z.Zhu, J.Sun, Z.Zhu, Q.Huang, M.Teng, and L.Niu (2002).
Purification, crystallization and preliminary X-ray crystallographic analysis of agkaggregin, a C-type lectin-like protein from Agkistrodon acutus venom.
  Acta Crystallogr D Biol Crystallogr, 58, 675-678.  
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.