PDBsum entry 2a45

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Hydrolase/hydrolase inhibitor PDB id
Jmol PyMol
Protein chains
32 a.a. *
258 a.a. *
48 a.a. *
52 a.a. *
40 a.a. *
44 a.a. *
0G6 ×2
PO4 ×2
* Residue conservation analysis
PDB id:
Name: Hydrolase/hydrolase inhibitor
Title: Crystal structure of the complex between thrombin and the ce region of fibrin
Structure: Thrombin light chain. Chain: a, d. Synonym: coagulation factor ii. Thrombin heavy chain. Chain: b, e. Synonym: coagulation factor ii. Fibrinogen alpha chain. Chain: g, j. Fragment: unp p02671, residues 36-92.
Source: Homo sapiens. Human. Organism_taxid: 9606. Other_details: proteolytic fragment. Other_details: proteolytic fragment
Biol. unit: Dodecamer (from PQS)
3.65Å     R-factor:   0.221     R-free:   0.290
Authors: I.Pechik,J.Madrazo,G.L.Gilliland,L.Medved
Key ref:
I.Pechik et al. (2006). Structural basis for sequential cleavage of fibrinopeptides upon fibrin assembly. Biochemistry, 45, 3588-3597. PubMed id: 16533041 DOI: 10.1021/bi0525369
27-Jun-05     Release date:   02-May-06    
Supersedes: 1qvh
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
622 a.a.
32 a.a.
Protein chains
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
622 a.a.
258 a.a.
Protein chains
Pfam   ArchSchema ?
P02671  (FIBA_HUMAN) -  Fibrinogen alpha chain
866 a.a.
48 a.a.
Protein chains
Pfam   ArchSchema ?
P02675  (FIBB_HUMAN) -  Fibrinogen beta chain
491 a.a.
52 a.a.
Protein chain
Pfam   ArchSchema ?
P02679  (FIBG_HUMAN) -  Fibrinogen gamma chain
453 a.a.
40 a.a.
Protein chain
Pfam   ArchSchema ?
P02679  (FIBG_HUMAN) -  Fibrinogen gamma chain
453 a.a.
44 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B, E, G: 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   2 terms 
  Biological process     signal transduction   5 terms 
  Biochemical function     receptor binding     4 terms  


DOI no: 10.1021/bi0525369 Biochemistry 45:3588-3597 (2006)
PubMed id: 16533041  
Structural basis for sequential cleavage of fibrinopeptides upon fibrin assembly.
I.Pechik, S.Yakovlev, M.W.Mosesson, G.L.Gilliland, L.Medved.
Nonsubstrate interaction of thrombin with fibrinogen promotes sequential cleavage of fibrinopeptides A and B (fpA and fpB, respectively) from the latter, resulting in its conversion into fibrin. The recently established crystal structure of human thrombin in complex with the central part of human fibrin clarified the mechanism of this interaction. Here, we reveal new details of the structure and present the results of molecular modeling of the fpA- and fpB-containing portions of the Aalpha and Bbeta chains, not identified in the complex, in both fibrinogen and protofibrils. The analysis of the results reveals that in fibrinogen the fpA-containing portions are in a more favorable position to bind in the active site cleft of bound thrombin. Surface plasmon resonance experiments establish that the fpB-containing portions interact with the fibrin-derived dimeric D-D fragment, suggesting that in protofibrils they bind to the newly formed DD regions bringing fpB into the vicinity of bound thrombin. These findings provide a coherent rationale for the preferential removal of fpA from fibrinogen at the first stage of fibrin assembly and the accelerated cleavage of fpB from protofibrils and/or fibrils at the second stage.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21106983 T.Riedel, J.Suttnar, E.Brynda, M.Houska, L.Medved, and J.E.Dyr (2011).
Fibrinopeptides A and B release in the process of surface fibrin formation.
  Blood, 117, 1700-1706.  
20676430 B.Apostolovic, M.Danial, and H.A.Klok (2010).
Coiled coils: attractive protein folding motifs for the fabrication of self-assembled, responsive and bioactive materials.
  Chem Soc Rev, 39, 3541-3575.  
19138790 K.C.Gersh, C.Nagaswami, J.W.Weisel, and S.T.Lord (2009).
The presence of gamma' chain impairs fibrin polymerization.
  Thromb Res, 124, 356-363.  
19036059 L.Medved, and J.W.Weisel (2009).
Recommendations for nomenclature on fibrinogen and fibrin.
  J Thromb Haemost, 7, 355-359.  
19289066 R.H.Abou-Saleh, S.D.Connell, R.Harrand, R.A.Ajjan, M.W.Mosesson, D.A.Smith, P.J.Grant, and R.A.Ariëns (2009).
Nanoscale probing reveals that reduced stiffness of clots from fibrinogen lacking 42 N-terminal Bbeta-chain residues is due to the formation of abnormal oligomers.
  Biophys J, 96, 2415-2427.  
18329094 E.Di Cera (2008).
  Mol Aspects Med, 29, 203-254.  
17606903 A.Bah, Z.Chen, L.A.Bush-Pelc, F.S.Mathews, and E.Di Cera (2007).
Crystal structures of murine thrombin in complex with the extracellular fragments of murine protease-activated receptors PAR3 and PAR4.
  Proc Natl Acad Sci U S A, 104, 11603-11608.
PDB codes: 2pux 2pv9
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.  
17681017 E.V.Lugovskoy, P.G.Gritsenko, L.G.Kapustianenko, I.N.Kolesnikova, V.I.Chernishov, and S.V.Komisarenko (2007).
Functional role of Bbeta-chain N-terminal fragment in the fibrin polymerization process.
  FEBS J, 274, 4540-4549.  
17922803 J.W.Weisel (2007).
Which knobs fit into which holes in fibrin polymerization?
  J Thromb Haemost, 5, 2340-2343.  
16940416 R.I.Litvinov, O.V.Gorkun, D.K.Galanakis, S.Yakovlev, L.Medved, H.Shuman, and J.W.Weisel (2007).
Polymerization of fibrin: Direct observation and quantification of individual B:b knob-hole interactions.
  Blood, 109, 130-138.  
18074396 R.L.Rich, and D.G.Myszka (2007).
Survey of the year 2006 commercial optical biosensor literature.
  J Mol Recognit, 20, 300-366.  
17287215 S.Piao, S.Kim, J.H.Kim, J.W.Park, B.L.Lee, and N.C.Ha (2007).
Crystal structure of the serine protease domain of prophenoloxidase activating factor-I.
  J Biol Chem, 282, 10783-10791.
PDB code: 2olg
17414213 S.T.Lord (2007).
Fibrinogen and fibrin: scaffold proteins in hemostasis.
  Curr Opin Hematol, 14, 236-241.  
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 codes are shown on the right.