title: A Light-Induced Reaction with Oxygen Leads to Chromophore Decomposition and Irreversible Photobleaching in GFP-Type Proteins.
abstract: Photobleaching and photostability of proteins of the green fluorescent protein (GFP) family are crucially important for practical applications of these widely used biomarkers. On the basis of simulations, we propose a mechanism for irreversible bleaching in GFP-type proteins under intense light illumination. The key feature of the mechanism is a photoinduced reaction of the chromophore with molecular oxygen (O2) inside the protein barrel leading to the chromophore's decomposition. Using quantum mechanics/molecular mechanics (QM/MM) modeling we show that a model system comprising the protein-bound Chro(-) and O2 can be excited to an electronic state of the intermolecular charge-transfer (CT) character (Chro(•)···O2(-•)). Once in the CT state, the system undergoes a series of chemical reactions with low activation barriers resulting in the cleavage of the bridging bond between the phenolic and imidazolinone rings and disintegration of the chromophore.
authors: †Department of Chemistry, M. V. Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow, 119991, Russian Federation.|‡N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygina 4, Moscow, 119334, Russian Federation.
authors: Bella L
authors: BL
authors: Grigorenko
authors: †Department of Chemistry, M. V. Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow, 119991, Russian Federation.|‡N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygina 4, Moscow, 119334, Russian Federation.
authors: Alexander V
authors: AV
authors: Nemukhin
authors: †Department of Chemistry, M. V. Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow, 119991, Russian Federation.
authors: Igor V
authors: IV
authors: Polyakov
authors: †Department of Chemistry, M. V. Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow, 119991, Russian Federation.
authors: Maria G
authors: MG
authors: Khrenova
authors: §Department of Chemistry, University of Southern California, Los Angeles, California 90089-0482, United States.
authors: Anna I
authors: AI
authors: Krylov
mesh_terms: D004579:Electron Transport; D049452:Green Fluorescent Proteins / Q000737:chemistry*; D008027:Light; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry*; D038761:Photobleaching; D017433:Protein Structure, Secondary; D011789:Quantum Theory; D017382:Reactive Oxygen Species / Q000737:chemistry
chemical_list: D017382:Reactive Oxygen Species; D049452:Green Fluorescent Proteins; D010100:Oxygen