Sub-nanosecond tryptophan radical deprotonation mediated by a protein-bound water cluster in class II DNA photolyases

Autor(en): Mueller, Pavel
Ignatz, Elisabeth
Kiontke, Stephan
Brettel, Klaus
Essen, Lars-Oliver
Stichwörter: ANIMAL 6-4 PHOTOLYASE; Chemistry; Chemistry, Multidisciplinary; CRYPTOCHROME; ELECTRON-TRANSFERRING TRYPTOPHAN; FAD; INTRAPROTEIN ELECTRON; MECHANISM; MODELS; PHOTOREDUCTION; REPAIR; SPECTROSCOPY
Erscheinungsdatum: 2018
Herausgeber: ROYAL SOC CHEMISTRY
Journal: CHEMICAL SCIENCE
Volumen: 9
Ausgabe: 5
Startseite: 1200
Seitenende: 1212
Zusammenfassung: 
Class II DNA photolyases are flavoenzymes occurring in both prokaryotes and eukaryotes including higher plants and animals. Despite considerable structural deviations from the well-studied class I DNA photolyases, they share the main biological function, namely light-driven repair of the most common UV-induced lesions in DNA, the cyclobutane pyrimidine dimers (CPDs). For DNA repair activity, photolyases require the fully reduced flavin adenine dinucleotide cofactor, FADH(-), which can be obtained from oxidized or semi-reduced FAD by a process called photoactivation. Using transient absorption spectroscopy, we have examined the initial electron and proton transfer reactions leading to photoactivation of the class II DNA photolyase from Methanosarcina mazei. Upon photoexcitation, FAD is reduced via a distinct (class II-specific) chain of three tryptophans, giving rise to an FAD(center dot-) TrpH(center dot+) radical pair. The distal Trp(388)H(center dot+) deprotonates to Trp(388)(center dot) in 350 ps, i.e., by three orders of magnitude faster than TrpH(center dot+) in aqueous solution or in any previously studied photolyase. We identified a class II-specific cluster of protein-bound water molecules ideally positioned to serve as the primary proton acceptor. The high rate of Trp(388)H(center dot+) deprotonation counters futile radical pair recombination and ensures efficient photoactivation.
ISSN: 20416520
DOI: 10.1039/c7sc03969g

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