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PDBsum entry 1eau
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protein ligands metals links
Hydrolase (serine protease) PDB id
1eau

 

 

 

 

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Contents
Protein chain
240 a.a. *
Ligands
SO4
BDK
Metals
_NA
Waters ×127
* Residue conservation analysis
PDB id:
1eau
Name: Hydrolase (serine protease)
Title: Nonpeptidic inhibitors of human leukocyte elastase. 6. Design of a potent, intratracheally active, pyridone-based trifluoromethyl ketone
Structure: Porcine pancreatic elastase. Chain: a. Engineered: yes
Source: Sus scrofa. Pig. Organism_taxid: 9823
Resolution:
2.00Å     R-factor:   0.161    
Authors: C.Ceccarelli
Key ref: P.R.Bernstein et al. (1995). Nonpeptidic inhibitors of human leukocyte elastase. 6. Design of a potent, intratracheally active, pyridone-based trifluoromethyl ketone. J Med Chem, 38, 212-215. PubMed id: 7837235 DOI: 10.1021/jm00001a028
Date:
22-Nov-94     Release date:   07-Feb-95    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00772  (CELA1_PIG) -  Chymotrypsin-like elastase family member 1 from Sus scrofa
Seq:
Struc: 		266 a.a.
240 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.36  - pancreatic elastase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of proteins, including elastin. Preferential cleavage: Ala-|-Xaa.

 

 
DOI no: 10.1021/jm00001a028 J Med Chem 38:212-215 (1995)
PubMed id: 7837235  
 
 
Nonpeptidic inhibitors of human leukocyte elastase. 6. Design of a potent, intratracheally active, pyridone-based trifluoromethyl ketone.
P.R.Bernstein, B.C.Gomes, B.J.Kosmider, E.P.Vacek, J.C.Williams.
 
  ABSTRACT  
 
Further modification of the 3-amino substituent in a trifluoromethyl ketone-based series of 3-amino-6-phenylpyridin-2-ones that had been optimized for oral activity led to analogs that were potent intratracheal inhibitors in a model of HLE-induced lung damage in the hamster. The best 3-amino substituent for intratracheal activity is [4-[N-[(4-chlorophenyl)sulfonyl]-carbamoyl]phenyl]sulfonyl. At a 30 min prechallenge interval, compound 9, which incorporates this substituent, had an ED50 of approximately 2 nmol/animal and, qualitatively, afforded a very similar dose-response relationship to that found with a peptidic trifluoromethyl ketone inhibitor, ICI 200,355.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
14517908 A.Nayeem, S.Krystek, and T.Stouch (2003).
An assessment of protein-ligand binding site polarizability.
  Biopolymers, 70, 201-211.  
12842041 W.K.Wang, V.Tereshko, P.Boccuni, D.MacGrogan, S.D.Nimer, and D.J.Patel (2003).
Malignant brain tumor repeats: a three-leaved propeller architecture with ligand/peptide binding pockets.
  Structure, 11, 775-789.
PDB codes: 1oyx 1oz2 1oz3
10733603 B.Macchia, D.Gentili, M.Macchia, F.Mamone, A.Martinelli, E.Orlandini, A.Rossello, G.Cercignani, R.Pierotti, M.Allegretti, C.Asti, and G.Caselli (2000).
Synthesis, inhibitory activity towards human leukocyte elastase and molecular modelling studies of 1-carbamoyl-4-methyleneaminoxyazetidinones.
  Eur J Med Chem, 35, 53-67.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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