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Transforming a Stable Amide into a Highly Reactive One: Capturing the Essence of Enzymatic Catalysis
Author(s) -
Souza Bruno S.,
Mora Jose R.,
Wanderlind Eduardo H.,
Clementin Rosilene M.,
Gesser Jose C.,
Fiedler Haidi D.,
Nome Faruk,
Menger Fredric M.
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201701306
Subject(s) - amide , enzyme , catalysis , chemistry , carboxylate , embedding , stereochemistry , organic chemistry , artificial intelligence , computer science
Aspartic proteinases, which include HIV‐1 proteinase, function with two aspartate carboxy groups at the active site. This relationship has been modeled in a system possessing an otherwise unactivated amide positioned between two carboxy groups. The model amide is cleaved at an enzyme‐like rate that renders the amide nonisolable at 35 °C and pH 4 owing to the joint presence of carboxy and carboxylate groups. A currently advanced theory attributing almost the entire catalytic power of enzymes to electrostatic reorganization is shown to be superfluous when suitable interatomic interactions are present. Our kinetic results are consistent with spatiotemporal concepts where embedding the amide group between two carboxylic moieties in proper geometries, at distances less than the diameter of water, leads to enzyme‐like rate enhancements. Space and time are the essence of enzyme catalysis.