The Role of Metal Complexation in the Unfolding Energetics of a Nudix Hydrolase

, intrapeptide and protein-water H-bonds, residue distances, active-site spread, and site-resolved metal coordination─along a steered coordinate pulling the protein apart. Our findings support a pathway-specific mechanism in which the duration of active-site coherence (compact spread and intact coordination) is the dominant predictor of mechanical/chemical stability. Along the pulling coordinate, residues Glu 117 and Thr40, and metal-sulfate interactions are also seen to be levers for stabilization or disruption.