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Structure and mechanism of a phage-encoded SAM lyase revises catalytic function of enzyme family

DOI: 10.7554/eLife.61818 DOI Help

Authors: Xiaohu Guo (Uppsala University) , Annika Soderholm (Uppsala University) , Sandesh Kanchugal Puttaswamy (Uppsala University) , Geir V Isaksen (Uppsala University; UiT - The Arctic University of Norway) , Omar Warsi (Uppsala University) , Ulrich Eckhard (Uppsala University) , Silvia Triguis (Uppsala University) , Adolf Gogoll (Uppsala University) , Jon Jerlström-hultqvist (Uppsala University) , Johan Åqvist (Uppsala University) , Dan I. Andersson (Uppsala University) , Maria Selmer (Uppsala University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Elife , VOL 10

State: Published (Approved)
Published: February 2021
Diamond Proposal Number(s): 11171

Open Access Open Access

Abstract: The 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.

Subject Areas: Biology and Bio-materials

Instruments: B21-High Throughput SAXS

Other Facilities: ID23-1 at ESRF


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