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PDBsum entry 3lu9

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
3lu9
Jmol
Contents
Protein chains
44 a.a. *
251 a.a. *
25 a.a. *
45 a.a. *
Ligands
NAG ×2
GOL
Metals
_NA ×2
Waters ×698
* Residue conservation analysis
PDB id:
3lu9
Name: Hydrolase
Title: Crystal structure of human thrombin mutant s195a in complex extracellular fragment of human par1
Structure: Prothrombin. Chain: a, d. Synonym: coagulation factor ii, activation peptide fragment activation peptide fragment 2, thrombin light chain, thromb chain. Engineered: yes. Mutation: yes. Prothrombin. Chain: b, e.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: f2, human. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Gene: f2. Gene: f2r, cf2r, par1, tr. Expression_system_taxid: 10029
Resolution:
1.80Å     R-factor:   0.195     R-free:   0.236
Authors: P.S.Gandhi,Z.Chen,E.Di Cera
Key ref: P.S.Gandhi et al. (2010). Crystal structure of thrombin bound to the uncleaved extracellular fragment of PAR1. J Biol Chem, 285, 15393-15398. PubMed id: 20236938
Date:
17-Feb-10     Release date:   16-Mar-10    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
Seq:
Struc:
 
Seq:
Struc:
622 a.a.
44 a.a.
Protein chains
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
Seq:
Struc:
 
Seq:
Struc:
622 a.a.
251 a.a.*
Protein chains
Pfam   ArchSchema ?
P25116  (PAR1_HUMAN) -  Proteinase-activated receptor 1
Seq:
Struc:
425 a.a.
25 a.a.
Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
Seq:
Struc:
 
Seq:
Struc:
622 a.a.
45 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, D, E: E.C.3.4.21.5  - 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  

 

 
J Biol Chem 285:15393-15398 (2010)
PubMed id: 20236938  
 
 
Crystal structure of thrombin bound to the uncleaved extracellular fragment of PAR1.
P.S.Gandhi, Z.Chen, E.Di Cera.
 
  ABSTRACT  
 
Abundant structural information exists on how thrombin recognizes ligands at the active site or at exosites separate from the active site region, but remarkably little is known about how thrombin recognizes substrates that bridge both the active site and exosite I. The case of the protease-activated receptor PAR1 is particularly relevant in view of the plethora of biological effects associated with its activation by thrombin. Here, we present the 1.8 A resolution structure of thrombin S195A in complex with a 30-residue long uncleaved extracellular fragment of PAR1 that documents for the first time a productive binding mode bridging the active site and exosite I. The structure reveals two unexpected features of the thrombin-PAR1 interaction. The acidic P3 residue of PAR1, Asp(39), does not hinder binding to the active site and actually makes favorable interactions with Gly(219) of thrombin. The tethered ligand domain shows a considerable degree of disorder even when bound to thrombin. The results fill a significant gap in our understanding of the molecular mechanisms of recognition by thrombin in ways that are relevant to other physiological substrates.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21360607 H.C.Castro, P.A.Abreu, R.B.Geraldo, R.C.Martins, R.Dos Santos, N.I.Loureiro, L.M.Cabral, and C.R.Rodrigues (2011).
Looking at the proteases from a simple perspective.
  J Mol Recognit, 24, 165-181.  
20836572 S.Leonardi, P.Tricoci, and R.C.Becker (2010).
Thrombin receptor antagonists for the treatment of atherothrombosis: therapeutic potential of vorapaxar and E-5555.
  Drugs, 70, 1771-1783.  
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