PDBsum entry 2hwl

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
27 a.a. *
251 a.a. *
33 a.a. *
14 a.a. *
_NA ×2
Waters ×133
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of thrombin in complex with fibrinogen gam peptide
Structure: Prothrombin. Chain: a, c. Fragment: thrombin light chain. Synonym: coagulation factor ii. Engineered: yes. Prothrombin. Chain: b, d. Fragment: thrombin heavy chain. Synonym: coagulation factor ii.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: f2. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_organ: kidney. Synthetic: yes. Other_details: the protein was chemically synthesized. The
Biol. unit: Pentamer (from PQS)
2.40Å     R-factor:   0.214     R-free:   0.249
Authors: A.O.Pineda,Z.W.Chen,F.Marino,F.S.Mathews,M.W.Mosesson,E.Di C
Key ref: A.O.Pineda et al. (2007). Crystal structure of thrombin in complex with fibrinogen gamma' peptide. Biophys Chem, 125, 556-559. PubMed id: 16962697 DOI: 10.1016/j.bpc.2006.08.005
01-Aug-06     Release date:   19-Sep-06    
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Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
622 a.a.
27 a.a.
Protein chains
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
622 a.a.
251 a.a.*
Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
622 a.a.
33 a.a.
Protein chain
Pfam   ArchSchema ?
P02679  (FIBG_HUMAN) -  Fibrinogen gamma chain
453 a.a.
14 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D: E.C.  - Thrombin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Arg-|-Gly; activates fibrinogen to fibrin and releases fibrinopeptide A and B.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     blood coagulation   2 terms 
  Biochemical function     catalytic activity     3 terms  


DOI no: 10.1016/j.bpc.2006.08.005 Biophys Chem 125:556-559 (2007)
PubMed id: 16962697  
Crystal structure of thrombin in complex with fibrinogen gamma' peptide.
A.O.Pineda, Z.W.Chen, F.Marino, F.S.Mathews, M.W.Mosesson, E.Di Cera.
Elevated levels of heterodimeric gamma(A)/gamma' fibrinogen 2 have been associated with an increased incidence of coronary artery disease, whereas a lowered content of gamma' chains is associated with an increased risk of venous thrombosis. Both situations may be related to the unique features of thrombin binding to variant gamma' chains. The gamma' peptide is an anionic fragment that binds thrombin with high affinity without interfering directly with substrate binding. Here we report the crystal structure of thrombin bound to the gamma' peptide, solved at 2.4 A resolution. The complex reveals extensive interactions between thrombin and the gamma' peptide mediated by electrostatic contacts with residues of exosite II and hydrophobic interactions with a pocket in close proximity to the Na(+) binding site. In its binding mode, the gamma' peptide completely overlaps with heparin bound to exosite II. These findings are consistent with functional data and broaden our understanding of how thrombin interacts with fibrinogen at the molecular level.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19589779 N.S.Petrera, A.R.Stafford, B.A.Leslie, C.A.Kretz, J.C.Fredenburgh, and J.I.Weitz (2009).
Long range communication between exosites 1 and 2 modulates thrombin function.
  J Biol Chem, 284, 25620-25629.  
19591434 T.M.Sabo, and M.C.Maurer (2009).
Biophysical investigation of GpIbalpha binding to thrombin anion binding exosite II.
  Biochemistry, 48, 7110-7122.  
18329094 E.Di Cera (2008).
  Mol Aspects Med, 29, 203-254.  
18055456 J.C.Fredenburgh, A.R.Stafford, B.A.Leslie, and J.I.Weitz (2008).
Bivalent Binding to {gamma}A/{gamma}'-Fibrin Engages Both Exosites of Thrombin and Protects It from Inhibition by the Antithrombin-Heparin Complex.
  J Biol Chem, 283, 2470-2477.  
18779330 S.Lancellotti, S.Rutella, V.De Filippis, N.Pozzi, B.Rocca, and R.De Cristofaro (2008).
Fibrinogen-elongated {gamma} Chain Inhibits Thrombin-induced Platelet Response, Hindering the Interaction with Different Receptors.
  J Biol Chem, 283, 30193-30204.  
17347701 E.Di Cera, M.J.Page, A.Bah, L.A.Bush-Pelc, and L.C.Garvey (2007).
Thrombin allostery.
  Phys Chem Chem Phys, 9, 1291-1306.  
17635727 E.Di Cera (2007).
Thrombin as procoagulant and anticoagulant.
  J Thromb Haemost, 5, 196-202.  
17414213 S.T.Lord (2007).
Fibrinogen and fibrin: scaffold proteins in hemostasis.
  Curr Opin Hematol, 14, 236-241.  
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