title: For enzymes, bigger is better.
abstract: Previously published data are re-examined in order to address two fundamental questions concerning enzyme catalysis: Why are enzymes so big? How is the substrate binding energy realized in the transition state? Relationships are shown that demonstrate (1) an increased enzyme:substrate mass ratio is associated with greater stabilization of the transition state and with increased substrate binding energy, and (2) tighter substrate binding is associated with greater transition state stabilization. It is argued that the conventional view of enzyme catalysis cannot account for these trends while the Shifting Specificity Model can. It is postulated that enzymes have evolved to be massive so that the interaction of the substrate with the active site alters the global conformation of the enzyme in a meaningful way; that is, the interaction alters the active site from an initial substrate-specific geometry to a transition state-specific geometry. It is also postulated that strong enzyme-substrate interactions better facilitate this active site transformation, thus, providing a mechanism for the realization of the substrate binding energy in the transition state of the chemical transformation.
authors.affiliation: Department of Chemistry, Baylor University, Waco, TX 76798, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Britt
mesh_terms: D002384:Catalysis; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008970:Molecular Weight; D013329:Structure-Activity Relationship
chemical_list: D004798:Enzymes