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PDBsum entry 3hat

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protein ligands Protein-protein interface(s) links
Hydrolase/hydrolase inhibitor PDB id
3hat
Jmol
Contents
Protein chains
36 a.a. *
251 a.a. *
Ligands
ASP-PHE-GLU-GLU-
ILE-PRO-GLU-GLU-
TYS-LEU
RNG-GLY-VAL-ARG
Waters ×179
* Residue conservation analysis
PDB id:
3hat
Name: Hydrolase/hydrolase inhibitor
Title: Active site mimetic inhibition of thrombin
Structure: Alpha-thrombin (small subunit). Chain: l. Alpha-thrombin (large subunit). Chain: h. Hirugen. Chain: i. Engineered: yes. Fpam (fibrinopeptide a mimic). Chain: t.
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: blood. Tissue: blood. Synthetic: yes
Biol. unit: Tetramer (from PQS)
Resolution:
2.50Å     R-factor:   0.140    
Authors: A.Tulinsky,I.I.Mathews
Key ref:
I.I.Mathews and A.Tulinsky (1995). Active-site mimetic inhibition of thrombin. Acta Crystallogr D Biol Crystallogr, 51, 550-559. PubMed id: 15299843 DOI: 10.1107/S0907444994013132
Date:
16-Oct-94     Release date:   27-Feb-95    
Supersedes: 2hat
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
Seq:
Struc:
 
Seq:
Struc:
622 a.a.
36 a.a.
Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
Seq:
Struc:
 
Seq:
Struc:
622 a.a.
251 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains L, H: 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  

 

 
DOI no: 10.1107/S0907444994013132 Acta Crystallogr D Biol Crystallogr 51:550-559 (1995)
PubMed id: 15299843  
 
 
Active-site mimetic inhibition of thrombin.
I.I.Mathews, A.Tulinsky.
 
  ABSTRACT  
 
The structures of two mimetic inhibitor complexes of human alpha-thrombin have been determined by X-ray crystallography. One mimics a beta-turn with a bicyclic ring system; the other mimics two different active-site binding modes. The beta-turn mimetic is used to approximate a turn found in the conformation of fibrinopeptide A, which is catalytically released by thrombin in the activation of fibrinogen to fibrin. The binding of the second mimetic is a hybrid between normal substrate and the abnormal binding of the potent natural leech inhibitor hirudin. The binding of the beta-turn mimetic is tenuous, because it is like a substrate, while that of the substrate-hirudin hybrid is that of a tenacious inhibitor (which it is). Structurally retrospect modifications for rational design and improvement of both mimetic inhibitors are proposed.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Thrombin peptide substrate- inhibitor complexes. The asterisk indicates sulfated tyrosine.
Figure 2.
Fig. 2. Mimetic inhibitors of thrombin. (a) FPAM, (b) DAPA, (c) FPAM 1. Special restraints applied to non-amino-acid groups during refinement to maintain geometry: arrow, bond distance; dotted, angle distance, double arrow, planar 1,4 distance and NB--B 1 --B3--B4, B2--B3--B5--NB in DAPA.
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1995, 51, 550-559) copyright 1995.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
9083110 F.R.Salemme, J.Spurlino, and R.Bone (1997).
Serendipity meets precision: the integration of structure-based drug design and combinatorial chemistry for efficient drug discovery.
  Structure, 5, 319-324.  
8913620 J.H.Matthews, R.Krishnan, M.J.Costanzo, B.E.Maryanoff, and A.Tulinsky (1996).
Crystal structures of thrombin with thiazole-containing inhibitors: probes of the S1' binding site.
  Biophys J, 71, 2830-2839.
PDB codes: 1a4w 1tbz
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