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De novo active sites for resurrected Precambrian enzymes
dc.contributor.author | Risso, Valeria Alejandra | |
dc.contributor.author | Martínez Rodríguez, Sergio | |
dc.contributor.author | Candel, Adela M. | |
dc.contributor.author | Krüger, Dennis M. | |
dc.contributor.author | Pantoja-Uceda, David | |
dc.contributor.author | Ortega Muñoz, Mariano | |
dc.contributor.author | Santoyo González, Francisco | |
dc.contributor.author | Gaucher, Eric A. | |
dc.contributor.author | Kamerlin, Shina C.L. | |
dc.contributor.author | Bruix, Marta | |
dc.contributor.author | Gavira, Jose A. | |
dc.contributor.author | Sánchez Ruiz, José Manuel | |
dc.date.accessioned | 2024-01-18T13:24:25Z | |
dc.date.available | 2024-01-18T13:24:25Z | |
dc.date.issued | 2017-07-18 | |
dc.identifier.citation | Risso, V., Martinez-Rodriguez, S., Candel, A. et al. De novo active sites for resurrected Precambrian enzymes. Nat Commun 8, 16113 (2017). https://doi.org/10.1038/ncomms16113 | es_ES |
dc.identifier.uri | https://hdl.handle.net/10481/86926 | |
dc.description | This work was supported by Feder Funds, Grants from the Spanish Ministry of Economy and Competitiveness BIO2015-66426-R (J.M.S.-R.), CSD2009-00088 (J.M.S.-R.), CTQ2011-29299-C02-01 (F.S.-G.), CTQ2011-22514 (M.B.), BIO2016-74875-P (J.A.G.), ‘Factorı´a Espan˜ola de Cristalizacion˜’, Consolider-Ingenio 2010 (J.A.G.) and CEI BioTic V19-2015 (V.A.R.), a Wallenberg Academy Fellowship (S.C.L.K.) and DuPont Young Professor Award (E.A.G.) and Grants NNX13AI08G and NNX13AI10G (E.A.G.) from NASA Exobiology. The European Research Council has provided financial support under the European Community’s Seventh Framework Programme (FP7/2007–2013)/ERC Grant Agreement No. 306474. We acknowledge the ESRF and ALBA for provision of synchrotron radiation time at beam lines ID29, ID23-1 and ID30A-1, and Xaloc, respectively, and the staff for their helpful support. Finally, we are grateful to the Swedish National Infrastructure for Computing (SNIC, 2015/16–12) for their generous provision of computational resources. | es_ES |
dc.description | Departamento de Quimica Fisica, Facultad de Ciencias University of Granada, 18071 Granada, Spain. 2Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, BMC Box 596, S-751 24 Uppsala, Sweden. 3Departamento de Quimica Fisica Biologica, Instituto de Quimica Fisica Rocasolano, CSIC, c/Serrano 119, 28006-Madrid, Spain. 4Departamento de Quimica Organica, Facultad de Ciencias University of Granada, 18071 Granada, Spain. 5School of Biology, School of Chemistry and Biochemistry, Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia 30322, USA. 6Laboratorio de Estudios Cristalograficos, Instituto Andaluz de Ciencias de la Tierra, CSIC-University of Granada Avenida de la Palmeras 4, Granada, 18100 Armilla, Spain. | es_ES |
dc.description.abstract | 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. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Springer Nature | es_ES |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.title | De novo active sites for resurrected Precambrian enzymes | es_ES |
dc.type | journal article | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.identifier.doi | 10.1038/ncomms16113 | |
dc.type.hasVersion | VoR | es_ES |