Excited-State Proton Transfer Can Tune the Color of Protein Fluorescent Markers.
We show by quantum mechanical/molecular mechanical (QM/MM) simulations that phenylbenzothiazoles undergoing an excited-state proton transfer (ESPT) can be used to probe protein binding sites. For 2-(2'-hydroxy-4'-aminophenyl)benzothiazole (HABT) bound to a tyrosine kinase, the absolute and relative intensities of the fluorescence bands arising from the enol and keto forms are found to be strongly dependent on the active-site conformation. The emission properties are tuned by hydrogen-bonding interactions of HABT with the neighboring amino acid T766 and with active-site water. The use of ESPT tuners opens the possibility of creating two-color fluorescent markers for protein binding sites, with potential applications in the detection of mutations in cancer cell lines.
Department of Chemistry, Federal University of Lavras, 37200-000, Lavras, Minas Gerais, Brazil.
Daiana T
DT
Mancini
Department of Chemistry, École Normale Supeŕieur, UMR ENS-CNRS-UPMC 8640, 24 rue Lhomond, 75005, Paris, France. kakali.sen@ens.fr.
Kakali
K
Sen
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, Germany. barbatti@kofo.mpg.de.
Mario
M
Barbatti
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, Germany.
Walter
W
Thiel
Department of Chemistry, Federal University of Lavras, 37200-000, Lavras, Minas Gerais, Brazil. teo@dqi.ufla.br.
Teodorico C
TC
Ramalho
D001665:Binding Sites; D020134:Catalytic Domain; D005456:Fluorescent Dyes / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D011522:Protons; D011789:Quantum Theory; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics; D013844:Thiazoles / Q000737:chemistry
D005456:Fluorescent Dyes; D011522:Protons; D013844:Thiazoles; D011494:Protein Kinases; C070845:2-phenylbenzothiazole
benzothiazole; enzyme inhibitors; molecular dynamics; photochemical reactions; proton transfer