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PDBsum entry 2r2m

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protein ligands Protein-protein interface(s) links
Hydrolase/hydrolase inhibitor PDB id
2r2m
Jmol PyMol
Contents
Protein chains
26 a.a.
249 a.a. *
11 a.a. *
Ligands
I50
Waters ×137
* Residue conservation analysis
PDB id:
2r2m
Name: Hydrolase/hydrolase inhibitor
Title: 2-(2-chloro-6-fluorophenyl)acetamides as potent thrombin inh
Structure: Thrombin light chain. Chain: a. Fragment: unp residues 334-359. Thrombin heavy chain. Chain: b. Engineered: yes. Hirudin-3a. Chain: h. Fragment: unp residues 55-65.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: f2. Hirudo medicinalis. Medicinal leech. Organism_taxid: 6421
Resolution:
2.10Å     R-factor:   0.168     R-free:   0.214
Authors: J.Spurlino
Key ref: L.Lee et al. (2007). 2-(2-Chloro-6-fluorophenyl)acetamides as potent thrombin inhibitors. Bioorg Med Chem Lett, 17, 6266-6269. PubMed id: 17889527 DOI: 10.1016/j.bmcl.2007.09.013
Date:
27-Aug-07     Release date:   26-Aug-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
Seq:
Struc:
 
Seq:
Struc:
622 a.a.
26 a.a.
Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
Seq:
Struc:
 
Seq:
Struc:
622 a.a.
249 a.a.
Protein chain
Pfam   ArchSchema ?
P09945  (HIRV2_HIRME) -  Hirudin variant-2 (Fragment)
Seq:
Struc:
72 a.a.
11 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: 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     calcium ion binding     2 terms  

 

 
DOI no: 10.1016/j.bmcl.2007.09.013 Bioorg Med Chem Lett 17:6266-6269 (2007)
PubMed id: 17889527  
 
 
2-(2-Chloro-6-fluorophenyl)acetamides as potent thrombin inhibitors.
L.Lee, K.D.Kreutter, W.Pan, C.Crysler, J.Spurlino, M.R.Player, B.Tomczuk, T.Lu.
 
  ABSTRACT  
 
2-(2-Chloro-6-fluorophenyl)acetamides having 2,2-difluoro-2-aryl/heteroaryl-ethylamine P3 and oxyguanidine P1 substituents are potent thrombin inhibitors (K(i)=0.9-33.9 nM). 2-(5-Chloro-pyridin-2-yl)-2,2-difluoroethylamine was the best P3 substituent, yielding the most potent inhibitor (K(i)=0.7 nM). Replacing the P3 heteroaryl group with a phenyl ring or replacing the difluoro substitution with dimethyl or cyclopropyl groups in the linker reduced the affinity for thrombin significantly. The aminopyridine P1s also provided an increase in potency.
 

 

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