2af2

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2af2

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Solution structure of disulfide reduced and copper depleted Human Superoxide Dismutase

OverviewOverview

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.

DiseaseDisease

Known disease associated with this structure: Amyotrophic lateral sclerosis, due to SOD1 deficiency OMIM:[147450]

About this StructureAbout this Structure

2AF2 is a Single protein structure of sequence from Homo sapiens with ZN as ligand. Active as Superoxide dismutase, with EC number 1.15.1.1 Full crystallographic information is available from OCA.

ReferenceReference

Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form., Banci L, Bertini I, Cantini F, D'Amelio N, Gaggelli E, J Biol Chem. 2006 Jan 27;281(4):2333-7. Epub 2005 Nov 14. PMID:16291742

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