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The catalytic sites of 20S proteasomes and their role in subunit maturation: A mutational and crystallographic study
Open accessAbstract
We present a biochemical and crystallographic characterization of active site mutants of the yeast 20S proteasome with the aim to characterize substrate cleavage specificity, subunit intermediate processing, and maturation. β1(Pre3), β2(Pup1), and β5(Pre2) are responsible for the postacidic, tryptic, and chymotryptic activity, respectively. The maturation of active subunits is independent of the presence of other active subunits and occurs by intrasubunit autolysis. The propeptides of β6(Pre7) and β7(Pre4) are intermediately processed to their final forms by β2(Pup1) in the wild-type enzyme and by β5(Pre2) and β1(Pre3) in the β2(Pup1) inactive mutants. A role of the propeptide of β1(Pre3) is to prevent acetylation and thereby inactivation. A gallery of proteasome mutants that contain active site residues in the context of the inactive subunits β3(Pup3), β6(Pre7), and β7(Pre4) show that the presence of Gly-1, Thr1, Asp17, Lys33, Ser129, Asp166, and Ser169 is not sufficient to generate activity.
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Cited by
Structural basis of water-specific transport through the AQP1 water channel
Sui, H., Han, B.-G., Lee, J. K., Walian, P., & Jap, B. K. (2001) · Nature · doi:10.1038/414872a · Cited by 1,166
Irreversible Inhibitors of Serine, Cysteine, and Threonine Proteases
Powers, J. C., Asgian, J. L., Ekici, Ö. D., & James, K. E. (2002) · Chemical Reviews · doi:10.1021/cr010182v · Cited by 1,090
The ubiquitin-proteasome system
Nandi, D., Tahiliani, P., Kumar, A., & Chandu, D. (2006) · Journal of Biosciences · doi:10.1007/bf02705243 · Cited by 758
Groll, M., Berkers, C. R., Ploegh, H. L., & Ovaa, H. (2006) · Structure · doi:10.1016/j.str.2005.11.019 · Cited by 473
Self-citationGroll, M., Kim, K. B., Kairies, N., Huber, R., & Crews, C. M. (2000) · Journal of the American Chemical Society · doi:10.1021/ja993588m · Cited by 304
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Metadata
- Authors
- Groll, M., Heinemeyer, W., Jäger, S., Ullrich, T., Bochtler, M., Wolf, D. H., & Huber, R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-09-28
- Volume
- 96
- Issue
- 20
- Pages
- 10976-10983
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1965790877
- Cited by
- 300
- References
- 0
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- green
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- Groll, M., Heinemeyer, W., Jäger, S., Ullrich, T., Bochtler, M., Wolf, D. H., & Huber, R. (1999). The catalytic sites of 20S proteasomes and their role in subunit maturation: A mutational and crystallographic study. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.96.20.10976
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