[Quantum chemistry analysis of the mechanism of action of proteolytic enzymes. II. Nucleophilic attack]

Mol Biol (Mosk). 1984 Nov-Dec;18(6):1576-82.
[Article in Russian]

Abstract

Dynamic systems, modelling the elementary act of nucleophilic attack on the carbonyl carbon atom of amide (N-methyl-acetamide) and ester (methylacetate) substrates by some compounds, simulating the nucleophilic group of various types proteases active site were calculated and analysed by the CNDO/2 method, namely: 1) methoxyanion and the methanol (serine proteases), 2) water molecule in the presence of formate anion (carboxylic proteases) and 3) mercaptide anion (CH3S-) (thiolic proteases). The formation of productive enzyme-substrate complex was shown not only to orient reactive groups of the enzyme and substrate, but also to activate it by induction of a certain degree of cleavable pyramidalization, as a result of the partial resonance stabilization energy loss.

MeSH terms

  • Chemical Phenomena
  • Chemistry, Physical
  • Peptide Hydrolases / metabolism*
  • Protons
  • Quantum Theory
  • Substrate Specificity

Substances

  • Protons
  • Peptide Hydrolases