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    Singlet-Oxygen-Induced Phospholipase A(2) Inhibition: A Major Role for Interfacial Tryptophan Dioxidation

    Year: 2021

    Journal: Chem.-Eur. J., Volume 27, OCT 21, page 14702–14710

    Authors: Nasri, Zahra; Memari, Seyedali; Wenske, Sebastian; Clemen, Ramona; Martens, Ulrike; Delcea, Mihaela; Bekeschus, Sander; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Wende, Kristian

    Organizations: German Federal Ministry of Education and Research (BMBF) [03Z22DN12, 03Z22Di1]

    Keywords: cold physical plasma; enzyme inhibition; plasma chemistry; protein modifications; reactive oxygen and nitrogen species

    Several studies have revealed that various diseases such as cancer have been associated with elevated phospholipase A(2) (PLA(2)) activity. Therefore, the regulation of PLA(2) catalytic activity is undoubtedly vital. In this study, effective inactivation of PLA(2) due to reactive species produced from cold physical plasma as a source to model oxidative stress is reported. We found singlet oxygen to be the most relevant active agent in PLA(2) inhibition. A more detailed analysis of the plasma-treated PLA(2) identified tryptophan 128 as a hot spot, rich in double oxidation. The significant dioxidation of this interfacial tryptophan resulted in an N-formylkynurenine product via the oxidative opening of the tryptophan indole ring. Molecular dynamics simulation indicated that the efficient interactions between the tryptophan residue and phospholipids are eliminated following tryptophan dioxidation. As interfacial tryptophan residues are predominantly involved in the attaching of membrane enzymes to the bilayers, tryptophan dioxidation and indole ring opening leads to the loss of essential interactions for enzyme binding and, consequently, enzyme inactivation.
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