PDBsum entry 1de7

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protein metals Protein-protein interface(s) links
Hydrolase/hydrolase substrate PDB id
Protein chains
28 a.a. *
249 a.a. *
26 a.a. *
11 a.a. *
_NA ×2
Waters ×479
* Residue conservation analysis
PDB id:
Name: Hydrolase/hydrolase substrate
Title: Interaction of factor xiii activation peptide with alpha-thr crystal structure of the enzyme-substrate complex
Structure: Alpha-thrombin (light chain). Chain: l, j. Alpha-thrombin (heavy chain). Chain: h, k. Factor xiii activation peptide (28-37). Chain: a, b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: plasma. Synthetic: yes
Biol. unit: Trimer (from PQS)
2.00Å     R-factor:   0.194     R-free:   0.257
Authors: C.Sadasivan,V.C.Yee
Key ref:
C.Sadasivan and V.C.Yee (2000). Interaction of the factor XIII activation peptide with alpha -thrombin. Crystal structure of its enzyme-substrate analog complex. J Biol Chem, 275, 36942-36948. PubMed id: 10956659 DOI: 10.1074/jbc.M006076200
13-Nov-99     Release date:   13-Dec-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
622 a.a.
28 a.a.
Protein chains
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
622 a.a.
249 a.a.
Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
622 a.a.
26 a.a.
Protein chains
No UniProt id for this chain
Struc: 11 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains L, H, J, K: 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: 10.1074/jbc.M006076200 J Biol Chem 275:36942-36948 (2000)
PubMed id: 10956659  
Interaction of the factor XIII activation peptide with alpha -thrombin. Crystal structure of its enzyme-substrate analog complex.
C.Sadasivan, V.C.Yee.
The serine protease thrombin proteolytically activates blood coagulation factor XIII by cleavage at residue Arg(37); factor XIII in turn cross-links fibrin molecules and gives mechanical stability to the blood clot. The 2.0-A resolution x-ray crystal structure of human alpha-thrombin bound to the factor XIII-(28-37) decapeptide has been determined. This structure reveals the detailed atomic level interactions between the factor XIII activation peptide and thrombin and provides the first high resolution view of this functionally important part of the factor XIII molecule. A comparison of this structure with the crystal structure of fibrinopeptide A complexed with thrombin highlights several important determinants of thrombin substrate interaction. First, the P1 and P2 residues must be compatible with the geometry and chemistry of the S1 and S2 specificity sites in thrombin. Second, a glycine in the P5 position is necessary for the conserved substrate conformation seen in both factor XIII-(28-37) and fibrinopeptide A. Finally, the hydrophobic residues, which occupy the aryl binding site of thrombin determine the substrate conformation further away from the catalytic residues. In the case of factor XIII-(28-37), the aryl binding site is shared by hydrophobic residues P4 (Val(34)) and P9 (Val(29)). A bulkier residue in either of these sites may alter the substrate peptide conformation.
  Selected figure(s)  
Figure 3.
Fig. 3. Schematic representation of van der Waals interactions ( 4 Å) of thrombin with fXIII -(28-37) PEP1 (top) and FPA (15) (bottom). Interactions with the underlined residues are observed only in the given complex.
Figure 6.
Fig. 6. Superposition of Val34 in fXIII -(28-37) and surrounding thrombin residues. (PEP1, red; PEP2, green; FPA, blue; PPACK, magenta). The presence of the Val34 side chain in fXIII-(28-37) makes a shift in surrounding thrombin residues.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 36942-36948) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20218626 M.A.Jadhav, G.Isetti, T.A.Trumbo, and M.C.Maurer (2010).
Effects of introducing fibrinogen Aalpha character into the factor XIII activation peptide segment.
  Biochemistry, 49, 2918-2924.  
19644995 C.Y.Koh, M.Kazimirova, P.A.Nuttall, and R.M.Kini (2009).
Noncompetitive inhibitor of thrombin.
  Chembiochem, 10, 2155-2158.  
19804366 M.D.Andersen, M.Kjalke, S.Bang, I.Lautrup-Larsen, P.Becker, A.S.Andersen, O.H.Olsen, and H.R.Stennicke (2009).
Coagulation factor XIII variants with altered thrombin activation rates.
  Biol Chem, 390, 1279-1283.  
19235177 M.I.Zavodszky, A.Rohatgi, J.R.Van Voorst, H.Yan, and L.A.Kuhn (2009).
Scoring ligand similarity in structure-based virtual screening.
  J Mol Recognit, 22, 280-292.  
18329094 E.Di Cera (2008).
  Mol Aspects Med, 29, 203-254.  
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.  
16988547 P.S.Wells, J.L.Anderson, M.A.Rodger, N.Carson, R.L.Grimwood, and S.P.Doucette (2006).
The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous thromboembolism?
  Blood Coagul Fibrinolysis, 17, 533-538.  
16102053 J.A.Huntington (2005).
Molecular recognition mechanisms of thrombin.
  J Thromb Haemost, 3, 1861-1872.  
15049836 G.Isetti, and M.C.Maurer (2004).
Probing thrombin's ability to accommodate a V34F substitution within the factor XIII activation peptide segment (28-41).
  J Pept Res, 63, 241-252.  
12005439 B.M.Beadle, I.Trehan, P.J.Focia, and B.K.Shoichet (2002).
Structural milestones in the reaction pathway of an amide hydrolase: substrate, acyl, and product complexes of cephalothin with AmpC beta-lactamase.
  Structure, 10, 413-424.
PDB codes: 1kvl 1kvm
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