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De novo design of catalytic proteins
Open accessAbstract
The de novo design of catalytic proteins provides a stringent test of our understanding of enzyme function, while simultaneously laying the groundwork for the design of novel catalysts. Here we describe the design of an O 2 -dependent phenol oxidase whose structure, sequence, and activity are designed from first principles. The protein catalyzes the two-electron oxidation of 4-aminophenol ( k cat / K M = 1,500 M ·1 ·min ·1 ) to the corresponding quinone monoimine by using a diiron cofactor. The catalytic efficiency is sensitive to changes of the size of a methyl group in the protein, illustrating the specificity of the design.
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Citations
Cited by
Benner, S. A., & Sismour, A. M. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1637 · Cited by 834
Principles for designing ideal protein structures
Koga, N., Tatsumi-Koga, R., Liu, G., Xiao, R., Acton, T. B., Montelione, G. T., & Baker, D. (2012) · Nature · doi:10.1038/nature11600 · Cited by 564
Protein Design: Toward Functional Metalloenzymes
Yu, F., Cangelosi, V. M., Zastrow, M. L., Tegoni, M., Plegaria, J. S., Tebo, A. G., Mocny, C. S., Ruckthong, L., Qayyum, H., & Pecoraro, V. L. (2014) · Chemical Reviews · doi:10.1021/cr400458x · Cited by 441
Protein Design by Directed Evolution
Jäckel, C., Kast, P., & Hilvert, D. (2008) · Annual Review of Biophysics · doi:10.1146/annurev.biophys.37.032807.125832 · Cited by 409
Hydrolytic catalysis and structural stabilization in a designed metalloprotein
Zastrow, M. L., Peacock, A. F. A., Stuckey, J. A., & Pecoraro, V. L. (2012) · Nature Chemistry · doi:10.1038/nchem.1201 · Cited by 355
Metadata
- Authors
- Kaplan, J., & DeGrado, W. F.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-08-03
- Volume
- 101
- Issue
- 32
- Pages
- 11566-11570
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2092102609
- Cited by
- 316
- References
- 0
- FWCI
- 8.98
- Type
- journal article
- Language
- en
- Open access
- green
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