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PDBsum entry 1k2i

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Hydrolase PDB id
1k2i
Jmol
Contents
Protein chain
236 a.a. *
Ligands
SO4
SN1
Waters ×134
* Residue conservation analysis
PDB id:
1k2i
Name: Hydrolase
Title: Crystal structure of gamma-chymotrypsin in complex with 7- hydroxycoumarin
Structure: Chymotrypsinogen a. Chain: 1. Ec: 3.4.21.1
Source: Bos taurus. Cattle. Organism_taxid: 9913
Biol. unit: Dimer (from PQS)
Resolution:
1.80Å     R-factor:   0.180     R-free:   0.200
Authors: U.Ghani,K.K.S.Ng,Atta-Ur-Rahman,M.I.Choudhary,N.Ullah,M.N.G.
Key ref:
U.Ghani et al. (2001). Crystal structure of gamma-chymotrypsin in complex with 7-hydroxycoumarin. J Mol Biol, 314, 519-525. PubMed id: 11846564 DOI: 10.1006/jmbi.2001.5148
Date:
27-Sep-01     Release date:   05-Dec-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00766  (CTRA_BOVIN) -  Chymotrypsinogen A
Seq:
Struc:
245 a.a.
236 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.1  - Chymotrypsin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Tyr-|-Xaa, Trp-|-Xaa, Phe-|-Xaa, Leu-|-Xaa.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     digestion   2 terms 
  Biochemical function     catalytic activity     6 terms  

 

 
DOI no: 10.1006/jmbi.2001.5148 J Mol Biol 314:519-525 (2001)
PubMed id: 11846564  
 
 
Crystal structure of gamma-chymotrypsin in complex with 7-hydroxycoumarin.
U.Ghani, K.K.Ng, Atta-ur-Rahman, M.I.Choudhary, N.Ullah, M.N.James.
 
  ABSTRACT  
 
The 1.8 A crystal structure of 7-hydroxycoumarin (7-HC) bound to chymotrypsin reveals that this inhibitor forms a planar cinnamate acyl-enzyme complex. The phenyl ring of the bound inhibitor forms numerous van der Waals contacts in the S1 pocket of the enzyme, with the p-hydroxyl group donating a hydrogen bond to the main-chain oxygen atom of Ser217, and the o-hydroxyl group forming a water-mediated hydrogen bond with the carbonyl oxygen of Val227. The structure of the acyl-enzyme complex suggests that the mechanism of inhibition of 7-HC involves nucleophilic attack by the Ser195 O(gamma) atom on the carbonyl carbon atom of the inhibitor, accompanied by the breaking of the 2-pyrone ring of the inhibitor, and leading to the formation of a cinnamate acyl-enzyme derivative via a tetrahedral transition state. Comparisons with structures of photoreversible cinnamates bound to chymotrypsin reveal that although 7-HC interacts with the enzyme in a similar fashion, the binding of 7-HC to chymotrypsin takes place in a productive conformation in contrast to the photoreversible cinnamates. In summary, the 7-HC-chymotrypsin complex provides basic insight into the inhibition of chymotrypsin by natural coumarins and provides a structural basis for the design of more potent mechanism-based inhibitors against a wide range of biologically important chymotrypsin-like enzymes.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. (a) Stereo view of the Sigma-A weighted 2|F[o]| -|F[c]| electron density map superimposed onto the refined modeled of the 7-HC-chymotrypsin complex in the active site region (contoured at 1s). (b) Stereo view of the Sigma-A weighted 2|F[o]| -|F[c]| electron density surrounding the bound inhibitor (contoured at 1s). These were made using xfit[29].
Figure 4.
Figure 4. The 7-HC-chymotrypsin complex (blue) superimposed onto the chymotrypsin complexes of photoreversible p-nitrophenyl o-hydroxy-a-methyl cinnamate (red) and p-nitrophenyl o-hydroxy-p-(diethylamino)- a-methyl cinnamate (green). Note that the carbonyl oxygen atoms of the photoreversible cinnamates are pointing away from the oxyanion hole of the enzyme (PDB codes 3GCH and 4GCH)[22].
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 314, 519-525) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21376071 D.d.e. .O.Toyama, E.B.Diz Filho, B.S.Cavada, B.A.da Rocha, S.C.de Oliveira, C.A.Cotrim, V.C.Soares, P.Delatorre, S.Marangoni, and M.H.Toyama (2011).
Umbelliferone induces changes in the structure and pharmacological activities of Bn IV, a phospholipase A(2) isoform isolated from Bothrops neuwiedi.
  Toxicon, 57, 851-860.  
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