Issue 1, 2023

Pt(iv) complex selectively oxidizes alpha-synuclein methionine as disclosed by NMR

Abstract

Alpha-synuclein (αS) is an intrinsically disordered neuronal protein, and the oxidative modification of αS promotes its oligomerization and accumulation in Parkinson's disease. By combining high-resolution NMR spectroscopy and mass spectrometry, we investigated the interaction of a platinum(IV) complex with αS at the residual specific resolution. The data indicate that the Pt(IV) complex was able to oxidize the methionine sidechains in a distinct manner under physiological conditions. The C-terminal M116 and M127 were first oxidized in a mutually exclusive manner followed by the oxidation of M5 with a large excess of Pt(IV), whereas M1 could not be oxidized. The oxidized methionines were unable to bind to Pt(II) and the Pt(II)-coordinated methionine could not be oxidized by H2O2. These results show the distinct oxidation preferences of αS methionines exhibited by the Pt(IV) complex at the residual specific resolution and imply the presence of long-range spatial contacts for the segments containing methionines in this intrinsically disordered protein.

Graphical abstract: Pt(iv) complex selectively oxidizes alpha-synuclein methionine as disclosed by NMR

Supplementary files

Article information

Article type
Research Article
Submitted
05 Aug 2022
Accepted
07 Nov 2022
First published
09 Nov 2022

Inorg. Chem. Front., 2023,10, 296-304

Pt(IV) complex selectively oxidizes alpha-synuclein methionine as disclosed by NMR

B. Pan, H. Liu, W. Meng and X. Su, Inorg. Chem. Front., 2023, 10, 296 DOI: 10.1039/D2QI01705A

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