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Higher-order epista...
Higher-order epistasis shapes the fitness landscape of a xenobiotic-degrading enzyme
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- Yang, Gloria (författare)
- Univ British Columbia, Michael Smith Labs, Vancouver, BC, Canada
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- Anderson, Dave W. (författare)
- Univ British Columbia, Michael Smith Labs, Vancouver, BC, Canada;Univ Calgary, Biochem & Mol Biol, Calgary, AB, Canada
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- Baier, Florian (författare)
- Univ British Columbia, Michael Smith Labs, Vancouver, BC, Canada
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- Dohmen, Elias (författare)
- Westfalische Wilhelms Univ, Inst Evolut & Biodivers, Evolutionary Bioinformat, Munster, Germany
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- Hong, Nansook (författare)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT, Australia
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- Carr, Paul D. (författare)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT, Australia
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- Kamerlin, Shina C. Lynn, 1981- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Biokemi
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- Jackson, Colin J. (författare)
- Australian Natl Univ, Res Sch Chem, Canberra, ACT, Australia
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- Bornberg-Bauer, Erich (författare)
- Westfalische Wilhelms Univ, Inst Evolut & Biodivers, Evolutionary Bioinformat, Munster, Germany
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- Tokuriki, Nobuhiko (författare)
- Univ British Columbia, Michael Smith Labs, Vancouver, BC, Canada
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(creator_code:org_t)
- 2019-10-21
- 2019
- Engelska.
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Ingår i: Nature Chemical Biology. - : NATURE PUBLISHING GROUP. - 1552-4450 .- 1552-4469. ; 15:11, s. 1120-1128
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Characterizing the adaptive landscapes that encompass the emergence of novel enzyme functions can provide molecular insights into both enzymatic and evolutionary mechanisms. Here, we combine ancestral protein reconstruction with biochemical, structural and mutational analyses to characterize the functional evolution of methyl-parathion hydrolase (MPH), an organophosphate-degrading enzyme. We identify five mutations that are necessary and sufficient for the evolution of MPH from an ancestral dihydrocoumarin hydrolase. In-depth analyses of the adaptive landscapes encompassing this evolutionary transition revealed that the mutations form a complex interaction network, defined in part by higher-order epistasis, that constrained the adaptive pathways available. By also characterizing the adaptive landscapes in terms of their functional activities towards three additional organophosphate substrates, we reveal that subtle differences in the polarity of the substrate substituents drastically alter the network of epistatic interactions. Our work suggests that the mutations function collectively to enable substrate recognition via subtle structural repositioning.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
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Yang, Gloria
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Anderson, Dave W ...
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Baier, Florian
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Dohmen, Elias
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Hong, Nansook
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Carr, Paul D.
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visa fler...
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Kamerlin, Shina ...
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Jackson, Colin J ...
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Bornberg-Bauer, ...
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Tokuriki, Nobuhi ...
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Uppsala universitet