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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Structural effects of stabilization and complexation of a zinc-deficient superoxide dismutase

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Manieri, Tania M. [1] ; Sensi, Stefano L. [2, 3, 4] ; Squitti, Rosanna [5] ; Cerchiaro, Giselle [1]
Total Authors: 4
[1] Fed Univ ABC UFABC, Ctr Nat Sci & Humanities, Ave Estados 5001, Bloco B, BR-09210580 Santo Andre, SP - Brazil
[2] Univ G dAnnunzio, Ctr Adv Studies & Technol CAST, Chieti - Italy
[3] Univ Calif Irvine, Dept Neurol, Inst Mind Impairments & Neurol Disorders iMIND, Irvine, CA 92717 - USA
[4] Univ Calif Irvine, Dept Pharmacol, Inst Mind Impairments & Neurol Disorders iMIND, Irvine, CA 92717 - USA
[5] IRCCS Ist Ctr San Giovanni Dio Fatebenefratelli, Brescia - Italy
Total Affiliations: 5
Document type: Journal article
Source: HELIYON; v. 7, n. 1 JAN 2021.
Web of Science Citations: 0

The activity of the erythrocyte Cu-2,Zn-2-superoxide dismutase (SOD1) is altered in Alzheimer's disease (AD) patients. These patients, compared to healthy subjects, exhibit low plasmatic zinc (Zn) levels in the presence of high plasmatic levels of copper (Cu). SOD1 is an antioxidant enzyme characterized by the presence of two metal ions, Cu and Zn, on its active site. On the SOD1, Cu exerts a catalytic role, and Zn serves a structural function. In this study, we generated a modified SOD1 characterized by an altered capacity to complex Zn. The study investigates the metal-binding dynamics of the enzyme, estimating the stability of a SOD1 protein lacking the appropriate Zn site complexation. Our mutant SOD1 possesses a double amino acid mutation (T135S and K136E) that interferes with the correct Zn site complexation. We found that the protein mutations produce unstable Zn coordination and lower enzymatic activity even when complexed with Cu. Analysis with circular dichroism (CD) spectra on metal titration showed a considerable difference between the two Zn entries in the native dimeric enzyme, and Cu presents a simultaneous entrance in the protein. Otherwise, the mutant T135S,K136E-SOD1 exhibited Zn and Cu complexation instability, being a useful in vitro model to study the SOD1 behavior in AD patients. (AU)

FAPESP's process: 12/24604-0 - Site-direct mutations on the metaloenzyme Cu,Zn-superoxide dismutase (SOD1): structural and functional aspects
Grantee:Tânia Maria Manieri
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 18/14152-0 - Studies for Prion Protein Cellular and metallic ions in oxidative stress
Grantee:Giselle Cerchiaro
Support Opportunities: Regular Research Grants