X-ray diffraction analysis of the inactivation of chymotrypsin by 3-benzyl-6-chloro-2-pyrone.
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.
D001665:Binding Sites; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D011487:Protein Conformation; D011714:Pyrans / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology*; D012694:Serine; D014961:X-Ray Diffraction / Q000379:methods
D011714:Pyrans; D011753:Pyrones; D012694:Serine; C037903:3-benzyl-6-chloro-2-pyrone; D002918:Chymotrypsin