title: Transforming a Stable Amide into a Highly Reactive One: Capturing the Essence of Enzymatic Catalysis.
abstract: 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.
authors.affiliation: Department of Chemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-900, Brazil.
authors.forename: Bruno S
authors.identifier: 0000-0001-7030-9271
authors.initials: BS
authors.lastname: Souza
authors.affiliation: Dpto. de Ingeniería Química, Universidad San Francisco de Quito, Ecuador.
authors.forename: Jose R
authors.identifier: 0000-0001-6128-9504
authors.initials: JR
authors.lastname: Mora
authors.affiliation: Department of Chemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-900, Brazil.
authors.forename: Eduardo H
authors.identifier: 0000-0002-0534-5898
authors.initials: EH
authors.lastname: Wanderlind
authors.affiliation: Food and Chemistry School, Universidade Federal do Rio Grande, Brazil.
authors.forename: Rosilene M
authors.initials: RM
authors.lastname: Clementin
authors.affiliation: Department of Chemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-900, Brazil.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Gesser
authors.affiliation: Department of Chemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-900, Brazil.
authors.forename: Haidi D
authors.initials: HD
authors.lastname: Fiedler
authors.affiliation: Department of Chemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-900, Brazil.
authors.forename: Faruk
authors.identifier: 0000-0001-8864-6807
authors.initials: F
authors.lastname: Nome
authors.affiliation: Department of Chemistry, Emory University, Atlanta, GA, 30322, USA.
authors.forename: Fredric M
authors.initials: FM
authors.lastname: Menger
mesh_terms: D000577:Amides / Q000737:chemistry / Q000378:metabolism*; D057055:Aspartic Acid Proteases / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D000077318:Density Functional Theory; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D015394:Molecular Structure
chemical_list: D000577:Amides; D057055:Aspartic Acid Proteases
keywords: homogeneous catalysis; kinetics; molecular modeling; reaction mechanisms; spatiotemporal theory