Low pH dimerization of chymotrypsin in solution.
The mechanism of the acid dimerization of alpha-chymotrypsin in solution was reexamined using a number of chemical derivatives. Blocking of the carboxyl of Tyr-146, while that of ASP-64 remained free, eliminated completely the ability of alpha-chymotrypsin to dimerize, as did methylation of His-57. O-Acetylation of Tyr-146 reduced the dimerization constant to that of gamma-chymotrypsin, and deacetylation of the other accessible tyrosines did not affect the dimerization. It is concluded that the mechanism proposed by Aune and Timasheff [Aune, K.C., and Timasheff, S.N.(1971) Biochemistry 10, 1609-1617] for the solution dimerization which involves the electrostatic interaction between the His-57 imidazolium ring and the terminal carboxyl of Tyr-146 is still most consistent with all the experimental observations. The interactions in dilute solution may differ somewhat from those observed in crystals. In particular, the two intermolecular bridges formed by sulfate ions in crystals cannot be present in solution.
D000107:Acetylation; D002268:Carboxypeptidases; D002918:Chymotrypsin; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D046911:Macromolecular Substances; D011487:Protein Conformation; D012492:Salts; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014443:Tyrosine
D046911:Macromolecular Substances; D012492:Salts; D014443:Tyrosine; D002268:Carboxypeptidases; D002918:Chymotrypsin