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

Guo, Xiaohu (author)
Uppsala universitet,Institutionen för cell- och molekylärbiologi
Söderholm, Annika (author)
Uppsala universitet,Strukturbiologi
Kanchugal Puttaswamy, Sandesh (author)
Uppsala universitet,Strukturbiologi
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Isaksen, Geir V (author)
Uppsala universitet,Institutionen för cell- och molekylärbiologi,UiT Arctic Univ Norway, Hylleraas Ctr Quantum Mol Sci, Dept Chem, Tromso, Norway
Warsi, Omar M. (author)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
Eckhard, Ulrich (author)
Uppsala universitet,Institutionen för cell- och molekylärbiologi
Trigüis, Silvia (author)
Uppsala universitet,Strukturbiologi
Gogoll, Adolf, 1957- (author)
Uppsala universitet,Organisk kemi
Jerlstrom-Hultqvist, Jon, 1982- (author)
Uppsala universitet,Mikrobiologi,Institutionen för medicinsk biokemi och mikrobiologi
Åqvist, Johan (author)
Uppsala universitet,Beräkningsbiologi och bioinformatik
Andersson, Dan I. (author)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
Selmer, Maria (author)
Uppsala universitet,Strukturbiologi
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 (creator_code:org_t)
eLife Sciences Publications Ltd, 2021
2021
English.
In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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 headings

NATURVETENSKAP  -- Biologi -- Strukturbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Structural Biology (hsv//eng)
NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Keyword

Biologi med inriktning mot strukturbiologi
Biology with specialization in Structural Biology

Publication and Content Type

ref (subject category)
art (subject category)

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