Protein dynamics of [Cu-Zn] superoxide dismutase (SOD1): How protein motions at the global and local levels impact the reactivity of SOD1

This work explores the pivotal role that protein mobility plays in facilitating the catalytic activity of Copper-Zinc superoxide dismutase (SOD1). Through both localized active site distortions and correlated domain movement, these motions enable the enzyme to adopt the conformations necessary to achieve both substrate delivery and efficient catalytic transformation. Structural and computational studies of a biomimetic model complex are used to probe the localized interactions between substrate and secondary sphere residues that play a role in guiding substrate to the active site, as well as facilitating the conformational changes necessary for substrate turnover. Normal mode analysis (NMA) of SOD1 demonstrates how collective domain motion influences key residues of the electrostatic loop (ESL), guiding substrate to the active site and facilitating the delivery of the conserved water network necessary for proton transfer. Secondary sphere interactions in a biomimetic model compound coupled with normal mode analysis of superoxide dismutase demonstrates how collective domain motion influences catalytic activity through conformational change and substrate guidance at the active site. [Display omitted] •Structural & computational studies of a biomimetic model for superoxide dismutase (SOD1)•Normal mode analysis of SOD1 shows collective domain motion influencing key residues.•Protein and model system motion analysis of substrate guidance at the active site