PDBsum entry 2v3h

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protein ligands metals Protein-protein interface(s) links
Hydrolase/hydrolase inhibitor PDB id
Protein chains
250 a.a. *
28 a.a. *
Waters ×392
* Residue conservation analysis
PDB id:
Name: Hydrolase/hydrolase inhibitor
Title: Thrombin with 3-cycle no f
Structure: Thrombin heavy chain. Chain: h. Fragment: catalytic, residues 364-620. Engineered: yes. Hirudin iia. Chain: i. Fragment: c-terminus, residues 56-65. Engineered: yes. Other_details: the n-terminal asp is des-amino - i.E. Succi
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: ovary. Synthetic: yes. Hirudo medicinalis. Medicinal leech.
1.79Å     R-factor:   0.175     R-free:   0.207
Authors: D.W.Banner,U.Obst
Key ref:
K.Müller et al. (2007). Fluorine in pharmaceuticals: looking beyond intuition. Science, 317, 1881-1886. PubMed id: 17901324 DOI: 10.1126/science.1131943
18-Jun-07     Release date:   24-Jun-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
622 a.a.
250 a.a.
Protein chain
Pfam   ArchSchema ?
P00734  (THRB_HUMAN) -  Prothrombin
622 a.a.
28 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains H, L: 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: 10.1126/science.1131943 Science 317:1881-1886 (2007)
PubMed id: 17901324  
Fluorine in pharmaceuticals: looking beyond intuition.
K.Müller, C.Faeh, F.Diederich.
Fluorine substituents have become a widespread and important drug component, their introduction facilitated by the development of safe and selective fluorinating agents. Organofluorine affects nearly all physical and adsorption, distribution, metabolism, and excretion properties of a lead compound. Its inductive effects are relatively well understood, enhancing bioavailability, for example, by reducing the basicity of neighboring amines. In contrast, exploration of the specific influence of carbon-fluorine single bonds on docking interactions, whether through direct contact with the protein or through stereoelectronic effects on molecular conformation of the drug, has only recently begun. Here, we review experimental progress in this vein and add complementary analysis based on comprehensive searches in the Cambridge Structural Database and the Protein Data Bank.
  Selected figure(s)  
Figure 3.
Fig. 3. (A) Aryl–OCHF[2] fragment ( = 19°) of roflumilast bound to phosphordiesterase 4 (table S1, entry 7) shows a multipolar C–F···C=O contact with the backbone amide of Trp332. (B) Aryl–OCF[3] fragment ( = 81°) of an inhibitor bound to the Ser protease trypsin (table S1, entry 13). Protein Cs are shown in gray (also applies to Fig. 5 and the SOM).
Figure 5.
Fig. 5. (A) Fluorine interacts favorably with peptidic N–H (ligand Cs in green) and C=O (ligand Cs in purple) moieties. (B) Fluorine undergoes dipolar interactions with side-chain amides of Gln and Asp (ligand Cs in yellow). (C) The C–F residue of a tricyclic inhibitor undergoes a multipolar interaction with the backbone C=O of Asn98 in the D pocket of thrombin (table S1, entry 23). (D) A dipolar N–H···F–C interaction induces the shown conformation of a thrombin inhibitor within the enzyme (fig. S3 and table S1, entry 22).
  The above figures are reprinted by permission from the AAAs: Science (2007, 317, 1881-1886) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

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PDB codes: 3nyp 3nz7
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PDB codes: 3nk8 3nkk
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PDB code: 2xg3
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Small molecules showing significant protection of mice against botulinum neurotoxin serotype A.
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Thermodynamic Optimisation in Drug Discovery: A Case Study using Carbonic Anhydrase Inhibitors.
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PDB codes: 2weg 2weh 2wej 2weo
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PDB codes: 3gml 3gmm 3gmn 3gmo 3gmp 3gmq 3gmr
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PDB codes: 3f53 3f5a 3f5e
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PDB codes: 3d39 3d3v
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Antidepressant specificity of serotonin transporter suggested by three LeuT-SSRI structures.
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PDB codes: 3gwu 3gwv 3gww
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A convenient chemo-enzymatic synthesis and 18F-labelling of both enantiomers of trans-1-toluenesulfonyloxymethyl-2-fluoromethyl-cyclopropane.
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Fluorine in medicinal chemistry.
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