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Allosteric cooperativity in protein kinase A
Open accessAbstract
Allosteric signaling in proteins requires long-range communication mediated by highly conserved residues, often triggered by ligand binding. In this article, we map the allosteric network in the catalytic subunit of protein kinase A using NMR spectroscopy. We show that positive allosteric cooperativity is generated by nucleotide and substrate binding during the transitions through the major conformational states: apo, intermediate, and closed. The allosteric network is disrupted by a single site mutation (Y204A), which also decouples the cooperativity of ligand binding. Because protein kinase A is the prototype for the entire kinome, these findings may serve as a paradigm for describing long-range coupling in other protein kinases.
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Cites
cAMP activation of PKA defines an ancient signaling mechanism
Das, R., Esposito, V., Abu-Abed, M., Anand, G. S., Taylor, S. S., & Melacini, G. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609033103 · Cited by 130
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Cited by
Cooperativity in Noncovalent Interactions
Mahadevi, A. S., & Sastry, G. N. (2016) · Chemical Reviews · doi:10.1021/cr500344e · Cited by 933
Allosteric regulation and catalysis emerge via a common route
Goodey, N. M., & Benkovic, S. J. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.98 · Cited by 667
Allostery: an illustrated definition for the ‘second secret of life’
Fenton, A. W. (2008) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2008.05.009 · Cited by 320
A conserved protonation-dependent switch controls drug binding in the Abl kinase
Shan, Y., Seeliger, M. A., Eastwood, M. P., Frank, F., Xu, H., Jensen, M. Ø., Dror, R. O., Kuriyan, J., & Shaw, D. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811223106 · Cited by 262
Controlling Allosteric Networks in Proteins
Dokholyan, N. V. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00544 · Cited by 260
Metadata
- Authors
- Masterson, L. R., Mascioni, A., Traaseth, N. J., Taylor, S. S., & Veglia, G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2008-01-15
- Volume
- 105
- Issue
- 2
- Pages
- 506-511
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2156232082
- Cited by
- 171
- References
- 1
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- green
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- Masterson, L. R., Mascioni, A., Traaseth, N. J., Taylor, S. S., & Veglia, G. (2008). Allosteric cooperativity in protein kinase A. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0709214104
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