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

DC FieldValueLanguage
dc.contributor.authorMueller, Pavel
dc.contributor.authorIgnatz, Elisabeth
dc.contributor.authorKiontke, Stephan
dc.contributor.authorBrettel, Klaus
dc.contributor.authorEssen, Lars-Oliver
dc.date.accessioned2021-12-23T16:20:07Z-
dc.date.available2021-12-23T16:20:07Z-
dc.date.issued2018
dc.identifier.issn20416520
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/13330-
dc.description.abstractClass 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.
dc.description.sponsorshipFrench Agence Nationale de la RechercheFrench National Research Agency (ANR) [ANR-12-BSV8-0001]; French Infrastructure for Integrated Structural Biology (FRISBI) [ANR-10-INSB-05-01]; Air Force Office of Scientific Research (AFOSR)United States Department of DefenseAir Force Office of Scientific Research (AFOSR) [FA9550-14-1-0409]; This work was supported by the French Agence Nationale de la Recherche (grant ANR-12-BSV8-0001), by the French Infrastructure for Integrated Structural Biology (FRISBI; grant ANR-10-INSB-05-01) and by the Air Force Office of Scientific Research (AFOSR; grant FA9550-14-1-0409).
dc.language.isoen
dc.publisherROYAL SOC CHEMISTRY
dc.relation.ispartofCHEMICAL SCIENCE
dc.subjectANIMAL 6-4 PHOTOLYASE
dc.subjectChemistry
dc.subjectChemistry, Multidisciplinary
dc.subjectCRYPTOCHROME
dc.subjectELECTRON-TRANSFERRING TRYPTOPHAN
dc.subjectFAD
dc.subjectINTRAPROTEIN ELECTRON
dc.subjectMECHANISM
dc.subjectMODELS
dc.subjectPHOTOREDUCTION
dc.subjectREPAIR
dc.subjectSPECTROSCOPY
dc.titleSub-nanosecond tryptophan radical deprotonation mediated by a protein-bound water cluster in class II DNA photolyases
dc.typejournal article
dc.identifier.doi10.1039/c7sc03969g
dc.identifier.isiISI:000424010600013
dc.description.volume9
dc.description.issue5
dc.description.startpage1200
dc.description.endpage1212
dc.contributor.orcid0000-0003-4272-4026
dc.contributor.orcid0000-0002-3245-0810
dc.contributor.researcheridL-3862-2016
dc.contributor.researcheridI-8299-2012
dc.identifier.eissn20416539
dc.publisher.placeTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND
dcterms.isPartOf.abbreviationChem. Sci.
dcterms.oaStatusGreen Submitted, gold, Green Published
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