The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Large shifts in pK a values of lysine residues buried inside a protein
Open accessAbstract
Internal ionizable groups in proteins are relatively rare but they are essential for catalysis and energy transduction. To examine molecular determinants of their unusual and functionally important properties, we engineered 25 variants of staphylococcal nuclease with lysine residues at internal positions. Nineteen of the Lys residues have depressed pK a values, some as low as 5.3, and 20 titrate without triggering any detectable conformational reorganization. Apparently, simply by being buried in the protein interior, these Lys residues acquired pK a values comparable to those of naturally occurring internal ionizable groups involved in catalysis and biological H + transport. The pK a values of some of the internal Lys residues were affected by interactions with surface carboxylic groups. The apparent polarizability reported by the pK a values varied significantly from location to location inside the protein. These data will enable an unprecedented examination of the positional dependence of the dielectric response of a protein. This study also shows that the ability of proteins to withstand the presence of charges in their hydrophobic interior is a fundamental property inherent to all stable proteins, not a specialized adaptation unique to proteins that evolved to depend on internal charges for function.
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Cites
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Self-citationRandom walk in orthogonal space to achieve efficient free-energy simulation of complex systems
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Charges in the hydrophobic interior of proteins
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The reactivity-driven biochemical mechanism of covalent KRASG12C inhibitors
Hansen, R., Peters, U., Babbar, A., Chen, Y., Feng, J., Janes, M. R., Li, L.-S., Ren, P., Liu, Y., & Zarrinkar, P. P. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0061-5 · Cited by 153
Beyond cysteine: recent developments in the area of targeted covalent inhibition
Mukherjee, H., & Grimster, N. P. (2018) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2018.05.011 · Cited by 95
Development of covalent inhibitors: Principle, design, and application in cancer
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Protein p K a Prediction with Machine Learning
Cai, Z., Luo, F., Wang, Y., Li, E., & Huang, Y. (2021) · ACS Omega · doi:10.1021/acsomega.1c05440 · Cited by 45
Metadata
- Authors
- Isom, D. G., Castañeda, C. A., Cannon, B. R., & García-Moreno E., B.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2011-03-09
- Volume
- 108
- Issue
- 13
- Pages
- 5260-5265
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2046385606
- Cited by
- 466
- References
- 24
- FWCI
- 9.87
- Type
- journal article
- Language
- en
- Open access
- green
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- Isom, D. G., Castañeda, C. A., Cannon, B. R., & García-Moreno E., B. (2011). Large shifts in pK a values of lysine residues buried inside a protein. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1010750108
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