X-ray diffraction analysis of the inactivation of chymotrypsin by 3-benzyl-6-chloro-2-pyrone

Biochemistry. 1986 Sep 23;25(19):5633-8. doi: 10.1021/bi00367a043.


The inactivation of chymotrypsin by 3-benzyl-6-chloro-2-pyrone has been studied. A covalent adduct is formed that deacylates slowly with a half-life of 23 h. X-ray diffraction analysis at 1.9-A resolution of the inactivator-enzyme complex shows that the gamma-oxygen of the active-site serine (serine-195) is covalently attached to C-1 of (Z)-2-benzylpentenedioic acid, the benzyl group of the inactivator is held in the hydrophobic specificity pocket of the enzyme, and the free carboxylate forms a salt bridge with the active-site histidine (histidine-57). The conformational changes that occur in the protein as a result of complexation are described. It is proposed that formation of the salt bridge prevents access of water and, therefore, hydrolysis of the acyl-enzyme.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Chymotrypsin / antagonists & inhibitors*
  • Models, Molecular
  • Protein Conformation
  • Pyrans / pharmacology*
  • Pyrones / pharmacology*
  • Serine
  • X-Ray Diffraction / methods


  • Pyrans
  • Pyrones
  • Serine
  • 3-benzyl-6-chloro-2-pyrone
  • Chymotrypsin