Multimodal response to copper binding in superoxide dismutase dynamics

Copper/zinc superoxide dismutase (SOD) is a homodimeric metalloenzyme which has been extensively studied as a bench-mark for structure-function relationships in proteins, in particular because of its implication in the familial form of the neu-rodegenerative disease amyotrophic lateral sclerosis. Here, we investigate microcrystalline preparations of two differently metallated forms of SOD, namely the fully mature functional CuI,Zn state and the E,Zn-SOD state in which the Cu site is empty. By using solid-state NMR with fast magic-angle spinning (MAS) at high magnetic fields (1H Larmor frequency of 800-1000 MHz), we quantify motions spanning a dynamic range from ns to ms. We determine that metal ion uptake does not act as a rigidification element but as a switch redistributing motional processes on different timescales, with coupling of the dynam-ics of histidine sidechains and those of remote key backbone elements of the protein.