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Regulation of an Enzyme by Phosphorylation at the Active Site
Abstract
The isocitrate dehydrogenase of Escherichia coli is an example of a ubiquitous class of enzymes that are regulated by covalent modification. In the three-dimensional structure of the enzyme-substrate complex, isocitrate forms a hydrogen bond with Ser 113 , the site of regulatory phosphorylation. The structures of Asp 113 and Glu 113 mutants, which mimic the inactivation of the enzyme by phosphorylation, show minimal conformational changes from wild type, as in the phosphorylated enzyme. Calculations based on observed structures suggest that the change in electrostatic potential when a negative charge is introduced either by phosphorylation or site-directed mutagenesis is sufficient to inactivate the enzyme. Thus, direct interaction at a ligand binding site is an alternative mechanism to induced conformational changes from an allosteric site in the regulation of protein activity by phosphorylation.
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Citations
Cited by
Reitman, Z. J., & Yan, H. (2010) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djq187 · Cited by 562
RIDER, M. H., BERTRAND, L., VERTOMMEN, D., MICHELS, P. A., ROUSSEAU, G. G., & HUE, L. (2004) · Biochemical Journal · doi:10.1042/bj20040752 · Cited by 440
Parker, D., Ferreri, K., Nakajima, T., Lamorte, V. J., Evans, R., Koerber, S. C., Hoeger, C., & Montminy, M. R. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.2.694 · Cited by 408
Xu, X., Zhao, J., Xu, Z., Peng, B., Huang, Q., Arnold, E., & Ding, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404298200 · Cited by 403
Global and Site-Specific Quantitative Phosphoproteomics: Principles and Applications
Macek, B., Mann, M., & Olsen, J. V. (2009) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.011008.145606 · Cited by 386
Metadata
- Authors
- Hurley, J. H., Dean, A. M., Sohl, J. L., Koshland, D. E., & Stroud, R. M.
- Venue
- Science
- Published
- 1990-08-31
- Volume
- 249
- Issue
- 4972
- Pages
- 1012-1016
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2011039500
- Cited by
- 249
- References
- 0
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- closed
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- Hurley, J. H., Dean, A. M., Sohl, J. L., Koshland, D. E., & Stroud, R. M. (1990). Regulation of an Enzyme by Phosphorylation at the Active Site. Science. https://doi.org/10.1126/science.2204109
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