4 years ago

Transforming a Stable Amide into a Highly Reactive One: Capturing the Essence of Enzymatic Catalysis

Transforming a Stable Amide into a Highly Reactive One: Capturing the Essence of Enzymatic Catalysis
Rosilene M. Clementin, Bruno S. Souza, Eduardo H. Wanderlind, Haidi D. Fiedler, Faruk Nome, Fredric M. Menger, Jose C. Gesser, Jose R. Mora
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. Solvent reorganization is not the sole source of enzymatic accelerations. As is shown in this Communication, two properly placed carboxy groups (see picture) can cause an otherwise nonactivated amide to cleave at enzymatic rates in the absence of any apparent solvent reorganization, thereby reaffirming spatiotemporal notions.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201701306

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