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Singlet‐Oxygen‐Induced Phospholipase A 2 Inhibition: A Major Role for Interfacial Tryptophan Dioxidation
Author(s) -
Nasri Zahra,
Memari Seyedali,
Wenske Sebastian,
Clemen Ramona,
Martens Ulrike,
Delcea Mihaela,
Bekeschus Sander,
Weltmann KlausDieter,
Woedtke Thomas,
Wende Kristian
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202102306
Subject(s) - tryptophan , indole test , singlet oxygen , chemistry , phospholipase a2 , enzyme , biophysics , biochemistry , reactive oxygen species , oxygen , stereochemistry , organic chemistry , biology , amino acid
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.