Structure and Function of Cholinesterases and Related Proteins

Abstract

Acetylcholinesterase (AChE) and chymotrypsin are serine enzymes whose catalytic mechanism involves a nucleophilic attack (serine) and a general acid-base moiety (histidine). The incipient imidiazolium which is formed as a result of the nucleophilic attack by serine is stabilized by the negatively charged carboxylate (Glu or Asp). This transition state stabilization is thought to be gained by a low-barrier hydrogen bond (LBHB) in which the proton is centrally located between N5 and the carboxylate oxygen.