Quantum chemistry analysis of the mechanism of action of proteolytic enzymes. II. Nucleophilic attack
Aleksandrov, S.L.; Antonov, V.K.
Molekuliarnaia Biologiia 18(6): 1576-1582
1984
ISSN/ISBN: 0026-8984 PMID: 6097813 Document Number: 225031
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.