PDBsum entry 1gmh

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Hydrolase(serine proteinase) PDB id
Protein chains
131 a.a. *
96 a.a. *
SO4 ×2
Waters ×102
* Residue conservation analysis
PDB id:
Name: Hydrolase(serine proteinase)
Title: Refined crystal structure of "aged" and "non-aged" organophosphoryl conjugates of gamma-chymotrypsin
Structure: Gamma-chymotrypsin a. Chain: e. Gamma-chymotrypsin a. Chain: f. Gamma-chymotrypsin a. Chain: g. Ec:
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organism_taxid: 9913
Biol. unit: Trimer (from PQS)
2.10Å     R-factor:   0.187    
Authors: M.Harel,J.L.Sussman,I.Silman
Key ref: M.Harel et al. (1991). Refined crystal structures of "aged" and "non-aged" organophosphoryl conjugates of gamma-chymotrypsin. J Mol Biol, 221, 909-918. PubMed id: 1942036
01-Jul-94     Release date:   30-Sep-94    
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Protein chain
Pfam   ArchSchema ?
P00766  (CTRA_BOVIN) -  Chymotrypsinogen A
245 a.a.
131 a.a.
Protein chain
Pfam   ArchSchema ?
P00766  (CTRA_BOVIN) -  Chymotrypsinogen A
245 a.a.
96 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains F, G: E.C.  - Chymotrypsin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Tyr-|-Xaa, Trp-|-Xaa, Phe-|-Xaa, Leu-|-Xaa.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     proteolysis   1 term 
  Biochemical function     catalytic activity     2 terms  


J Mol Biol 221:909-918 (1991)
PubMed id: 1942036  
Refined crystal structures of "aged" and "non-aged" organophosphoryl conjugates of gamma-chymotrypsin.
M.Harel, C.T.Su, F.Frolow, Y.Ashani, I.Silman, J.L.Sussman.
"Aged" organophosphoryl conjugates of serine hydrolases differ from the corresponding "non-aged" conjugates in their striking resistance to nucleophilic reactivation. The refined X-ray structures of "aged" and "non-aged" organophosphoryl conjugates of gamma-chymotrypsin were compared in order to understand the molecular basis for this resistance of "aged" conjugates. "Aged" and "non-aged" crystalline organophosphoryl-gamma-chymotrypsin conjugates were obtained by prolonged soaking of native gamma-chymotrypsin crystals with appropriate organophosphates. Thus, a representative "non-aged" conjugate, diethylphosphoryl-gamma-chymotrypsin, was obtained by soaking native crystals with paraoxon (diethyl-p-nitrophenyl phosphate), and a closely related "aged" conjugate, monoisopropyl-gamma-chymotrypsin, was obtained by soaking with diisopropylphosphorofluoridate. In both crystalline conjugates, the refined structures clearly reveal a high occupancy of the active site by the appropriate organophosphoryl moiety within covalent bonding distance of Ser195 O gamma. Whereas in the "non-aged" conjugate both ethyl groups can be visualized clearly, in the putative "aged" conjugate, as expected, only one isopropyl group is present. There is virtually no difference between the "aged" and "non-aged" conjugates either with respect to the conformation of the polypeptide backbone as a whole or with respect to the positioning of the side-chains within the active site. In the "aged" conjugate, however, close proximity (2.6 A) of the negatively charged phosphate oxygen atom of the dealkylated organophosphoryl group to His57 N epsilon 2 indicates the presence of a salt bridge between these two moieties. In contrast, in the "non-aged" conjugate the DEP moiety retains its two alkyl groups; thus, lacking a negative oxygen atom, it does not enter into such a charge-charge interaction and its nearest oxygen atom is 3.6 A away from His57 N epsilon 2. It is suggested that steric constraints imposed by the salt bridge in the "aged" conjugate lie at the basis of its resistance to reactivation.

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20056576 C.M.Thompson, J.M.Prins, and K.M.George (2010).
Mass spectrometric analyses of organophosphate insecticide oxon protein adducts.
  Environ Health Perspect, 118, 11-19.  
20004171 P.Masson, and O.Lockridge (2010).
Butyrylcholinesterase for protection from organophosphorus poisons: catalytic complexities and hysteretic behavior.
  Arch Biochem Biophys, 494, 107-120.  
19271773 T.M.Epstein, U.Samanta, S.D.Kirby, D.M.Cerasoli, and B.J.Bahnson (2009).
Crystal structures of brain group-VIII phospholipase A2 in nonaged complexes with the organophosphorus nerve agents soman and sarin.
  Biochemistry, 48, 3425-3435.
PDB codes: 3dt6 3dt8 3dt9
17372355 M.Sherawat, P.Kaur, M.Perbandt, C.Betzel, W.A.Slusarchyk, G.S.Bisacchi, C.Chang, B.L.Jacobson, H.M.Einspahr, and T.P.Singh (2007).
Structure of the complex of trypsin with a highly potent synthetic inhibitor at 0.97 A resolution.
  Acta Crystallogr D Biol Crystallogr, 63, 500-507.
PDB code: 2ayw
7766682 D.Aslanian, P.Gróf, F.Renault, and P.Masson (1995).
Raman spectroscopic study of conjugates of butyrylcholinesterase with organophosphates.
  Biochim Biophys Acta, 1249, 37-44.  
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