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Single-molecule paleoenzymology probes the chemistry of resurrected enzymes
Open accessAbstract
It is possible to travel back in time at the molecular level by reconstructing proteins from extinct organisms. Here we report the reconstruction, based on sequence predicted by phylogenetic analysis, of seven Precambrian thioredoxin enzymes (Trx) dating back between ~1.4 and ~4 billion years (Gyr). The reconstructed enzymes are up to 32 °C more stable than modern enzymes, and the oldest show markedly higher activity than extant ones at pH 5. We probed the mechanisms of reduction of these enzymes using single-molecule force spectroscopy. From the force dependency of the rate of reduction of an engineered substrate, we conclude that ancient Trxs use chemical mechanisms of reduction similar to those of modern enzymes. Although Trx enzymes have maintained their reductase chemistry unchanged, they have adapted over 4 Gyr to the changes in temperature and ocean acidity that characterize the evolution of the global environment from ancient to modern Earth.
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Cites
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Directed Evolution of Protein Catalysts
Zeymer, C., & Hilvert, D. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-012034 · Cited by 454
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The Role of Conformational Dynamics and Allostery in Modulating Protein Evolution
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Metadata
- Authors
- Perez-Jimenez, R., Inglés-Prieto, A., Zhao, Z.-M., Sanchez-Romero, I., Alegre-Cebollada, J., Kosuri, P., Garcia-Manyes, S., Kappock, T. J., Tanokura, M., Holmgren, A., Sanchez-Ruiz, J. M., Gaucher, E. A., & Fernandez, J. M.
- Venue
- Nature Structural & Molecular Biology
- Published
- 2011-04-03
- Volume
- 18
- Issue
- 5
- Pages
- 592-596
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2122940069
- Cited by
- 201
- References
- 6
- FWCI
- 5.53
- Type
- journal article
- Language
- en
- Open access
- green
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- Perez-Jimenez, R., Inglés-Prieto, A., Zhao, Z.-M., Sanchez-Romero, I., Alegre-Cebollada, J., Kosuri, P., Garcia-Manyes, S., Kappock, T. J., Tanokura, M., Holmgren, A., Sanchez-Ruiz, J. M., Gaucher, E. A., & Fernandez, J. M. (2011). Single-molecule paleoenzymology probes the chemistry of resurrected enzymes. Nature Structural & Molecular Biology. https://doi.org/10.1038/nsmb.2020
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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