The reactivity of individual solvent-coupled protein configurations is used to track and resolve the progress coordinate for the core reaction sequence of substrate radical rearrangement and hydrogen atom transfer in the ethanolamine ammonia-lyase (EAL) enzyme from Salmonella enterica. The first-order decay of the substrate radical intermediate is the monitored reaction. Heterogeneous confinement from sucrose hydrates in the mesophase solvent surrounding the cryotrapped protein introduces distributed kinetics in the non-native decay of the substrate radical pair capture substate, which arise from an ensemble of configurational microstates. Reaction rates increase by >103-fold across the distribution to approach that for the native enabled substate for radical rearrangement, which reacts with monotonic kinetics. The native progress coordinate thus involves a collapse of the configuration space to generate optimized reactivity. Reactivity tracking reveals fundamental features of solvent-protein-reaction configurational coupling and leads to a model that refines the ensemble paradigm of enzyme catalysis for strongly adiabatic chemical steps.