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PDBsum entry 1dlk

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protein ligands metals Protein-protein interface(s) links
Hydrolase/hydrolase inhibitor PDB id
1dlk
Jmol
Contents
Protein chains
13 a.a.
230 a.a. *
Ligands
PHQ-GLY-GLY-HPH-
0QE
×2
Metals
_CL
Waters ×281
* Residue conservation analysis
PDB id:
1dlk
Name: Hydrolase/hydrolase inhibitor
Title: Crystal structure analysis of delta-chymotrypsin bound to a chloromethyl ketone inhibitor
Structure: Thrombin light chain. Chain: a, c. Fragment: residues 1-13. Thrombin heavy chain. Chain: b, d. Fragment: residues 16-245. Peptidic inhibitor. Chain: e, f. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organ: pancreas. Synthetic: yes. Other_details: this sequence was synthetically constructed
Biol. unit: Dimer (from PQS)
Resolution:
2.14Å     R-factor:   0.206     R-free:   0.245
Authors: A.Mac Sweeney,G.Birrane,M.A.Walsh,T.O'Connell,J.P.G.Malthous
Key ref:
A.Mac Sweeney et al. (2000). Crystal structure of delta-chymotrypsin bound to a peptidyl chloromethyl ketone inhibitor. Acta Crystallogr D Biol Crystallogr, 56, 280-286. PubMed id: 10713514 DOI: 10.1107/S0907444999016583
Date:
10-Dec-99     Release date:   03-May-00    
PROCHECK
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 Headers
 References

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

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D: 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: 10.1107/S0907444999016583 Acta Crystallogr D Biol Crystallogr 56:280-286 (2000)
PubMed id: 10713514  
 
 
Crystal structure of delta-chymotrypsin bound to a peptidyl chloromethyl ketone inhibitor.
A.Mac Sweeney, G.Birrane, M.A.Walsh, T.O'Connell, J.P.Malthouse, T.M.Higgins.
 
  ABSTRACT  
 
Chymotrypsin is a member of the trypsin family of serine proteases and is one of the first proteins successfully studied by X-ray crystallography. It is secreted into the intestine as the inactive precursor chymotrypsinogen; four sequential cleavages of the peptide bonds following residues 13, 15, 146 and 148 occur to generate the active pi, delta, kappa and alpha forms of chymotrypsin. (13)C NMR that when the delta form of chymotrypsin is inhibited by 2-(13)C-enriched benzyloxycarbonylglycylglycylphenylalanyl chloromethane, a tetrahedral adduct is formed which is thought to be analogous to the tetrahedral intermediate formed during catalysis. This inhibitor complex has been crystallized as a dimer in space group P4(1)2(1)2. The structure has been refined at 2.14 A resolution to an R value of 21.2% (free R = 25.2%). Conformational differences between delta-chymotrypsin and chymotrypsinogen in the region of the flexible autolysis loop (residues 145-150) were observed. This is the first crystal structure of delta-chymotrypsin and includes two residues which are disordered in previous crystal structures of active chymotrypsin. A difference of 11.3 A(2) between the average B values of the monomers within the asymmetric unit is caused by lattice-disordering effects approximating to rotation of the molecules about a crystallographic screw axis. The substrate-binding mode of the inhibitor was similar to other chymotrypsin peptidyl inhibitor complexes, but this is the first published chymotrypsin structure in which the tetrahedral chloromethyl ketone transition-state analogue is observed. This structure is compared with that of a similar tetrahedral transition-state analogue which does not alkylate the active-site histidine residue.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Activation scheme of chymotrypsinogen.
Figure 5.
Figure 5 A comparison of the structures of the tetrahedral adducts formed when chymotrypsin is inhibited by (a) Z-Gly-Gly-(2-13C)Phe-CH[2]Cl and (b) Z-Leu-Phe-CF[3].
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2000, 56, 280-286) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20659345 Y.J.Jin, X.Zhang, C.Y.Cai, and S.J.Burakoff (2010).
Alkylating HIV-1 Nef - a potential way of HIV intervention.
  AIDS Res Ther, 7, 26.  
17213185 E.Spink, S.Cosgrove, L.Rogers, C.Hewage, and J.P.Malthouse (2007).
13C and 1H NMR studies of ionizations and hydrogen bonding in chymotrypsin-glyoxal inhibitor complexes.
  J Biol Chem, 282, 7852-7861.  
12787446 M.A.Biasutti, A.Posadaz, and N.A.García (2003).
A comparative kinetic study on the singlet molecular oxygen-mediated photoxidation of alpha- and beta-chymotrypsins.
  J Pept Res, 62, 11-18.  
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