Structural characterization of chemically stabilized, ALS-associated variants of Cu, Zn Superoxide Dismutase.

摘要

We present a rational, structure-based approach to SOD1 dimer stabilization that aims to form a single, intersubunit crosslink between two closely spaced cysteine residues. The specificity of this approach is high due to the combination of: 1) the uniquely high nucleophilicity of cysteine residues, 2) the tuning of cross-linker length for this particular task, and 3) the entropic advantage of a cross-linker bound to one cysteine binding the cysteine of an adjacent monomer. High specificity is an important determinant of cytotoxicity.