A role for conformational changes in enzyme catalysis

Biophys J. 2024 May 3:S0006-3495(24)00310-2. doi: 10.1016/j.bpj.2024.04.030. Online ahead of print.ABSTRACTThe role played by conformational changes in enzyme catalysis is controversial. In addition to examining specific enzymes, studying formal models can help identify the conditions under which conformational changes promote catalysis. Here, we present a model demonstrating how conformational changes can break a generic trade-off due to the conflicting requirements of successive steps in catalytic cycles, namely high specificity for the transition state to accelerate the chemical transformation and low affinity for the products to favor their release. The mechanism by which the trade-off is broken is a transition between conformations with different affinities for the substrate. The role of the effector that induces the transition is played by a substrate "handle", a part of the substrate that is not chemically transformed but whose interaction with the enzyme is nevertheless essential to rapidly complete the catalytic cycle. A key element of the model is the formalization of the constraints causing the trade-off that the presence of multiple states breaks, which we attribute to the strong chemical similarity between successive reaction states - substrates, transition states and products. For the sake of clarity, we present our model for irreversible one-step unimolecular reactions. In this context, we demonstrate how the different forms that chemical similarities between r...

Source: Biophysical Journal - May 5, 2024 Category: Physics Authors: Olivier Rivoire Source Type: research