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De novo active site...
De novo active sites for resurrected Precambrian enzymes
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- Risso, Valeria A. (författare)
- Univ Granada, Fac Ciencias, Dept Quim Fis, E-18071 Granada, Spain.
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- Martinez-Rodriguez, Sergio (författare)
- Univ Granada, Fac Ciencias, Dept Quim Fis, E-18071 Granada, Spain.
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- Candel, Adela M. (författare)
- Univ Granada, Fac Ciencias, Dept Quim Fis, E-18071 Granada, Spain.
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- Krüger, Dennis M. (författare)
- Uppsala universitet,Struktur- och molekylärbiologi,Science for Life Laboratory, SciLifeLab
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- Pantoja-Uceda, David (författare)
- CSIC, Inst Quim Fis Rocasolano, Dept Quim Fis Biol, C Serrano 119, E-28006 Madrid, Spain.
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- Ortega-Munoz, Mariano (författare)
- Univ Granada, Fac Ciencias, Dept Quim Organ, E-18071 Granada, Spain.
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- Santoyo-Gonzalez, Francisco (författare)
- Univ Granada, Fac Ciencias, Dept Quim Organ, E-18071 Granada, Spain.
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- Gaucher, Eric A. (författare)
- Georgia Inst Technol, Sch Biol, Sch Chem & Biochem, Parker H Petit Inst Bioengn & Biosci, Atlanta, GA 30322 USA.
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- Kamerlin, Shina C. Lynn, 1981- (författare)
- Uppsala universitet,Struktur- och molekylärbiologi,Science for Life Laboratory, SciLifeLab
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- Bruix, Marta (författare)
- CSIC, Inst Quim Fis Rocasolano, Dept Quim Fis Biol, C Serrano 119, E-28006 Madrid, Spain.
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- Gavira, Jose A. (författare)
- Univ Granada, CSIC, Inst Andaluz Ciencias Tierra, Lab Estudios Cristalog, Ave la Palmeras 4, Granada 18100, Armilla, Spain.
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- Sanchez-Ruiz, Jose M. (författare)
- Univ Granada, Fac Ciencias, Dept Quim Fis, E-18071 Granada, Spain.
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Univ Granada, Fac Ciencias, Dept Quim Fis, E-18071 Granada, Spain Struktur- och molekylärbiologi (creator_code:org_t)
- 2017-07-18
- 2017
- Engelska.
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://doi.org/10.1...
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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
- Protein engineering studies often suggest the emergence of completely new enzyme functionalities to be highly improbable. However, enzymes likely catalysed many different reactions already in the last universal common ancestor. Mechanisms for the emergence of completely new active sites must therefore either plausibly exist or at least have existed at the primordial protein stage. Here, we use resurrected Precambrian proteins as scaffolds for protein engineering and demonstrate that a new active site can be generated through a single hydrophobic-to-ionizable amino acid replacement that generates a partially buried group with perturbed physico-chemical properties. We provide experimental and computational evidence that conformational flexibility can assist the emergence and subsequent evolution of new active sites by improving substrate and transition-state binding, through the sampling of many potentially productive conformations. Our results suggest a mechanism for the emergence of primordial enzymes and highlight the potential of ancestral reconstruction as a tool for protein engineering.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
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- art (ämneskategori)
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- Av författaren/redakt...
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Risso, Valeria A ...
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Martinez-Rodrigu ...
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Candel, Adela M.
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Krüger, Dennis M ...
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Pantoja-Uceda, D ...
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Ortega-Munoz, Ma ...
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visa fler...
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Santoyo-Gonzalez ...
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Gaucher, Eric A.
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Kamerlin, Shina ...
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Bruix, Marta
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Gavira, Jose A.
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Sanchez-Ruiz, Jo ...
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visa färre...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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Nature Communica ...
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Uppsala universitet