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PDBsum entry 1whe

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protein links
Glycoprotein PDB id
1whe
Jmol
Contents
Protein chain
86 a.a.
PDB id:
1whe
Name: Glycoprotein
Title: Coagulation factor, nmr, 20 structures
Structure: Coagulation factor x. Chain: a. Other_details: the apo form of the fragment containing the terminal egf-like module
Source: Bos taurus. Cattle. Organism_taxid: 9913
NMR struc: 20 models
Authors: M.Sunnerhagen,G.A.Olah,J.Stenflo,S.Forsen,T.Drakenberg,J.Tre
Key ref:
M.Sunnerhagen et al. (1996). The relative orientation of Gla and EGF domains in coagulation factor X is altered by Ca2+ binding to the first EGF domain. A combined NMR-small angle X-ray scattering study. Biochemistry, 35, 11547-11559. PubMed id: 8794734 DOI: 10.1021/bi960633j
Date:
18-Jun-96     Release date:   15-May-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00743  (FA10_BOVIN) -  Coagulation factor X
Seq:
Struc:
492 a.a.
86 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 13 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: 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 
  Biochemical function     calcium ion binding     1 term  

 

 
DOI no: 10.1021/bi960633j Biochemistry 35:11547-11559 (1996)
PubMed id: 8794734  
 
 
The relative orientation of Gla and EGF domains in coagulation factor X is altered by Ca2+ binding to the first EGF domain. A combined NMR-small angle X-ray scattering study.
M.Sunnerhagen, G.A.Olah, J.Stenflo, S.Forsén, T.Drakenberg, J.Trewhella.
 
  ABSTRACT  
 
Coagulation factor X is a serine protease containing three noncatalytic domains: an N-terminal gamma-carboxyglutamic acid (Gla)1 domain followed by two epidermal growth factor (EGF)-like domains. The isolated N-terminal EGF domain binds Ca2+ with a Kd of 10(-3) M. When linked to the Gla domain, however, its Ca2+ affinity is increased 10-fold. In this paper, we present the NMR solution structure of the factor X Gla-EGF domain pair with Ca2+ bound to the EGF domain, as well as small angle X-ray scattering (SAXS) data on the Gla-EGF domain pair with and without Ca2+. Our results show that Ca2+ binding to the EGF domain makes the Gla and EGF domains fold toward each other using the Ca2+ site as a hinge. Presumably, a similar mechanism may be responsible for alterations in the relative orientation of protein domains in many other extracellular proteins containing EGF domains with the consensus for Ca2+ binding. The results of the NMR and SAXS measurements reported in this paper confirm our previous result that the Gla domain is folded also in its apo state when linked to the EGF domain [Sunnerhagen, M., et al. (1995) Nat. Struct. Biol. 2, 504-509]. Finally, our study clearly demonstrates the powerful combination of NMR and SAXS in the study of modular proteins, since this enables reliable evaluation of both short-range (NMR) and long-range interactions (SAXS).
 

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.  
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.  
18008171 A.Grishaev, V.Tugarinov, L.E.Kay, J.Trewhella, and A.Bax (2008).
Refined solution structure of the 82-kDa enzyme malate synthase G from joint NMR and synchrotron SAXS restraints.
  J Biomol NMR, 40, 95.
PDB code: 2jqx
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.  
18624698 M.J.Kwon, K.Y.Yoo, H.J.Kim, and S.H.Kim (2008).
Identification of mutations in the F9 gene including exon deletion by multiplex ligation-dependent probe amplification in 33 unrelated Korean patients with haemophilia B.
  Haemophilia, 14, 1069-1075.  
17292917 D.Lee, J.D.Walsh, P.Yu, M.A.Markus, T.Choli-Papadopoulou, C.D.Schwieters, S.Krueger, D.E.Draper, and Y.X.Wang (2007).
The structure of free L11 and functional dynamics of L11 in free, L11-rRNA(58 nt) binary and L11-rRNA(58 nt)-thiostrepton ternary complexes.
  J Mol Biol, 367, 1007-1022.
PDB codes: 2e34 2e35 2e36 2h8w
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.  
15381708 L.Garrigue-Antar, V.François, and K.E.Kadler (2004).
Deletion of epidermal growth factor-like domains converts mammalian tolloid into a chordinase and effective procollagen C-proteinase.
  J Biol Chem, 279, 49835-49841.  
12814644 B.R.Lentz (2003).
Exposure of platelet membrane phosphatidylserine regulates blood coagulation.
  Prog Lipid Res, 42, 423-438.  
14579355 B.V.Norledge, R.J.Petrovan, W.Ruf, and A.J.Olson (2003).
The tissue factor/factor VIIa/factor Xa complex: a model built by docking and site-directed mutagenesis.
  Proteins, 53, 640-648.
PDB code: 1nl8
12871416 K.E.Knobe, K.E.Persson, E.Sjörin, B.O.Villoutreix, J.Stenflo, and R.C.Ljung (2003).
Functional analysis of the EGF-like domain mutations Pro55Ser and Pro55Leu, which cause mild hemophilia B.
  J Thromb Haemost, 1, 782-790.  
14556624 M.J.Wood, L.A.Becvar, J.H.Prieto, G.Melacini, and E.A.Komives (2003).
NMR structures reveal how oxidation inactivates thrombomodulin.
  Biochemistry, 42, 11932-11942.  
11867437 D.Venkateswarlu, L.Perera, T.Darden, and L.G.Pedersen (2002).
Structure and dynamics of zymogen human blood coagulation factor X.
  Biophys J, 82, 1190-1206.  
11910037 X.Xu, Q.Liu, H.Yu, and Y.Xie (2002).
Ca(II)- and Tb(III)-induced stabilization and refolding of anticoagulation factor I from the venom of Agkistrodon acutus.
  Protein Sci, 11, 944-956.  
10861387 A.Häfner, F.Merola, G.Duportail, R.Hutterer, F.W.Schneider, and M.Hof (2000).
Calcium-induced conformational change in fragment 1-86 of factor X.
  Biopolymers, 57, 226-234.  
10617609 P.H.Celie, P.J.Lenting, and K.Mertens (2000).
Hydrophobic contact between the two epidermal growth factor-like domains of blood coagulation factor IX contributes to enzymatic activity.
  J Biol Chem, 275, 229-234.  
10091600 C.Valcarce, I.Björk, and J.Stenflo (1999).
The epidermal growth factor precursor. A calcium-binding, beta-hydroxyasparagine containing modular protein present on the surface of platelets.
  Eur J Biochem, 260, 200-207.  
10223294 K.E.Knobe, A.Berntsdotter, L.Shen, J.Morser, B.Dahlbäck, and B.O.Villoutreix (1999).
Probing the activation of protein C by the thrombin-thrombomodulin complex using structural analysis, site-directed mutagenesis, and computer modeling.
  Proteins, 35, 218-234.  
10092586 N.M.Thielens, K.Enrie, M.Lacroix, M.Jaquinod, J.F.Hernandez, A.F.Esser, and G.J.Arlaud (1999).
The N-terminal CUB-epidermal growth factor module pair of human complement protease C1r binds Ca2+ with high affinity and mediates Ca2+-dependent interaction with C1s.
  J Biol Chem, 274, 9149-9159.  
10353820 Y.H.Kao, G.F.Lee, Y.Wang, M.A.Starovasnik, R.F.Kelley, M.W.Spellman, and L.Lerner (1999).
The effect of O-fucosylation on the first EGF-like domain from human blood coagulation factor VII.
  Biochemistry, 38, 7097-7110.
PDB codes: 1f7e 1f7m 1ff7 1ffm
9692950 A.Muranyi, B.E.Finn, G.P.Gippert, S.Forsén, J.Stenflo, and T.Drakenberg (1998).
Solution structure of the N-terminal EGF-like domain from human factor VII.
  Biochemistry, 37, 10605-10615.
PDB code: 1bf9
9477945 B.Bersch, J.F.Hernandez, D.Marion, and G.J.Arlaud (1998).
Solution structure of the epidermal growth factor (EGF)-like module of human complement protease C1r, an atypical member of the EGF family.
  Biochemistry, 37, 1204-1214.
PDB code: 1apq
9667926 J.Evenäs, A.Malmendal, and S.Forsén (1998).
Calcium.
  Curr Opin Chem Biol, 2, 293-302.  
9618463 K.Kamata, H.Kawamoto, T.Honma, T.Iwama, and S.H.Kim (1998).
Structural basis for chemical inhibition of human blood coagulation factor Xa.
  Proc Natl Acad Sci U S A, 95, 6630-6635.
PDB codes: 1xka 1xkb
9268343 A.K.Sabharwal, K.Padmanabhan, A.Tulinsky, A.Mathur, J.Gorka, and S.P.Bajaj (1997).
Interaction of calcium with native and decarboxylated human factor X. Effect of proteolysis in the autolysis loop on catalytic efficiency and factor Va binding.
  J Biol Chem, 272, 22037-22045.  
9211891 C.R.Kelly, C.D.Dickinson, and W.Ruf (1997).
Ca2+ binding to the first epidermal growth factor module of coagulation factor VIIa is important for cofactor interaction and proteolytic function.
  J Biol Chem, 272, 17467-17472.  
9242658 E.Persson, O.H.Olsen, A.Ostergaard, and L.S.Nielsen (1997).
Ca2+ binding to the first epidermal growth factor-like domain of factor VIIa increases amidolytic activity and tissue factor affinity.
  J Biol Chem, 272, 19919-19924.  
9345630 J.Trewhella (1997).
Insights into biomolecular function from small-angle scattering.
  Curr Opin Struct Biol, 7, 702-708.  
  9336830 M.D.Rand, A.Lindblom, J.Carlson, B.O.Villoutreix, and J.Stenflo (1997).
Calcium binding to tandem repeats of EGF-like modules. Expression and characterization of the EGF-like modules of human Notch-1 implicated in receptor-ligand interactions.
  Protein Sci, 6, 2059-2071.  
9310374 Y.Stenberg, K.Julenius, I.Dahlqvist, T.Drakenberg, and J.Stenflo (1997).
Calcium-binding properties of the third and fourth epidermal-growth-factor-like modules in vitamin-K-dependent protein S.
  Eur J Biochem, 248, 163-170.  
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.