Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/5195
Title: Human SOD1 before Harboring the Catalytic Metal: solution structure of copper-depleted, disulfide-reduced form
Authors: L., Banci
I., Bertini
F., Cantini
N., D'Amelio
Gaggelli, Elena 
Keywords: amyotrophic-lateral-sclerosis; zinc superoxide-dismutase; protein nmr; free cysteine; torsion angle dynamics; chaperone; mutants
Issue Date: 2006
Project: None 
Journal: THE JOURNAL OF BIOLOGICAL CHEMISTRY
Abstract: 
SOD1 has to undergo several post-translational modifications before reaching its mature form. The protein requires insertion of zinc and copper atoms, followed by the formation of a conserved S-S bond between Cys-57 and Cys-146 (human numbering), which makes the protein fully active. In this report an NMR structural investigation of the reduced SH-SH form of thermostable E, Zn-as-SOD1 (E is empty; as is C6A, C111S) is reported, characterizing the protein just before the last step leading to the mature form. The structure is compared with that of the oxidized S-S form as well as with that of the yeast SOD1 complexed with its copper chaperone, CCS. Local conformational rearrangements upon disulfide bridge reduction are localized in the region near Cys-57 that is completely exposed to the solvent in the present structure, at variance with the oxidized forms. There is a local disorder around Cys-57 that may serve for protein-protein recognition and may possibly be involved in intermolecular S-S bonds in familial amyotrophic lateral sclerosis-related SOD1 mutants. The structure allows us to further discuss the copper loading mechanism in SOD1.
Description: 
18197
URI: http://hdl.handle.net/20.500.12779/5195
ISSN: 0021-9258
DOI: 10.1074/jbc.M506497200
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