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dc.contributor.authorIsaksen, Geir Villy
dc.contributor.authorGuo, Xiaohu
dc.contributor.authorSöderholm, Annika
dc.contributor.authorKanchugal P, Sandesh
dc.contributor.authorWarsi, Omar
dc.contributor.authorEckhard, Ulrich
dc.contributor.authorSilvia, Trigüis
dc.contributor.authorGogoll, Adolf
dc.contributor.authorJerlström-Hultqvist, Jon
dc.contributor.authorÅqvist, Johan
dc.contributor.authorAnderson, Dan I
dc.contributor.authorSelmer, Maria
dc.date.accessioned2021-02-16T10:05:49Z
dc.date.available2021-02-16T10:05:49Z
dc.date.issued2021-02-10
dc.description.abstractThe first S-adenosyl methionine (SAM) degrading enzyme (SAMase) was discovered in bacteriophage T3, as a counter-defense against the bacterial restriction-modification system, and annotated as a SAM hydrolase forming 5’ methyl-thioadenosine (MTA) and L-homoserine. From environmental phages, we recently discovered three SAMases with barely detectable sequence similarity to T3 SAMase and without homology to proteins of known structure. Here, we present the very first phage SAMase structures, in complex with a substrate analogue and the product MTA. The structure shows a trimer of alpha–beta sandwiches similar to the GlnB-like superfamily, with active sites formed at the trimer interfaces. Quantum-mechanical calculations, thin-layer chromatography, and nuclear magnetic resonance spectroscopy demonstrate that this family of enzymes are not hydrolases but lyases forming MTA and L-homoserine lactone in a unimolecular reaction mechanism. Sequence analysis and in vitro and in vivo mutagenesis support that T3 SAMase belongs to the same structural family and utilizes the same reaction mechanism.en_US
dc.identifier.citationIsaksen GVI, Guo, Söderholm, Kanchugal P, Warsi, Eckhard, Silvia, Gogoll A, Jerlström-Hultqvist J, Åqvist J, Anderson, Selmer. Structure and mechanism of a phage-encoded SAM lyase revises catalytic function of enzyme family. eLIFE. 2021en_US
dc.identifier.cristinIDFRIDAID 1888734
dc.identifier.doihttps://doi.org/10.7554/eLife.61818
dc.identifier.issn2050-084X
dc.identifier.urihttps://hdl.handle.net/10037/20576
dc.language.isoengen_US
dc.publishereLife Sciences Publicationsen_US
dc.relation.journaleLIFE
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/SFF/262695/Norway/Hylleraas Centre for Quantum Molecular Sciences//en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRINATEK/274858/Norway/Evolutionary Principles of Biocatalysts From Extreme Environments//en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.subjectVDP::Mathematics and natural science: 400::Chemistry: 440en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Kjemi: 440en_US
dc.titleStructure and mechanism of a phage-encoded SAM lyase revises catalytic function of enzyme familyen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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