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The Glutathione Transferase Structural Family Includes a Nuclear Chloride Channel and a Ryanodine Receptor Calcium Release Channel Modulator
Open accessAbstract
The ubiquitous glutathione transferases (GSTs) catalyze glutathione conjugation to many compounds and have other diverse functions that continue to be discovered. We noticed sequence similarities between Omega class GSTs and a nuclear chloride channel, NCC27 (CLIC1), and show here that NCC27 belongs to the GST structural family. The structural homology prompted us to investigate whether the human Omega class glutathione transferase GSTO1-1 forms or modulates ion channels. We find that GSTO1-1 modulates ryanodine receptors (RyR), which are calcium channels in the endoplasmic reticulum of various cells. Cardiac RyR2 activity was inhibited by GSTO1-1, whereas skeletal muscle RyR1 activity was potentiated. An enzymatically active conformation of GSTO1-1 was required for inhibition of RyR2, and mutation of the active site cysteine (Cys-32 --> Ala) abolished the inhibitory activity. We propose a novel role for GSTO1-1 in protecting cells containing RyR2 from apoptosis induced by Ca(2+) mobilization from intracellular stores.
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Cites
A new approach to protein fold recognition
Jones, D. T., Taylort, W. R., & Thornton, J. M. (1992) · Nature · doi:10.1038/358086a0 · Cited by 1,221
Cited by
SHEEHAN, D., MEADE, G., FOLEY, V. M., & DOWD, C. A. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3600001 · Cited by 3,057
Molecular Structure and Physiological Function of Chloride Channels
Jentsch, T. J., Stein, V., Weinreich, F., & Zdebik, A. A. (2002) · Physiological Reviews · doi:10.1152/physrev.00029.2001 · Cited by 1,256
Phylogenies of glutathione transferase families
Pearson, W. R. (2005) · Methods in Enzymology · doi:10.1016/s0076-6879(05)01012-8 · Cited by 105
Skvortsov, S., Sarg, B., Loeffler-Ragg, J., Skvortsova, I., Lindner, H., Werner Ott, H., Lukas, P., Illmensee, K., & Zwierzina, H. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.1551.3.12 · Cited by 33
Metadata
- Authors
- Dulhunty, A., Gage, P., Curtis, S., Chelvanayagam, G., & Board, P.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-02
- Volume
- 276
- Issue
- 5
- Pages
- 3319-3323
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1976690731
- Cited by
- 279
- References
- 1
- FWCI
- 6.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Dulhunty, A., Gage, P., Curtis, S., Chelvanayagam, G., & Board, P. (2001). The Glutathione Transferase Structural Family Includes a Nuclear Chloride Channel and a Ryanodine Receptor Calcium Release Channel Modulator. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m007874200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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