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Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates
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| Zeitschriftentitel: | Bioscience Reports |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , |
| In: | Bioscience Reports, 33, 2013, 1 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Portland Press Ltd.
|
| Schlagwörter: |
| author_facet |
Langendorf, Christopher G. Tuck, Kellie L. Key, Trevor L. G. Fenalti, Gustavo Pike, Robert N. Rosado, Carlos J. Wong, Anders S. M. Buckle, Ashley M. Law, Ruby H. P. Whisstock, James C. Langendorf, Christopher G. Tuck, Kellie L. Key, Trevor L. G. Fenalti, Gustavo Pike, Robert N. Rosado, Carlos J. Wong, Anders S. M. Buckle, Ashley M. Law, Ruby H. P. Whisstock, James C. |
|---|---|
| author |
Langendorf, Christopher G. Tuck, Kellie L. Key, Trevor L. G. Fenalti, Gustavo Pike, Robert N. Rosado, Carlos J. Wong, Anders S. M. Buckle, Ashley M. Law, Ruby H. P. Whisstock, James C. |
| spellingShingle |
Langendorf, Christopher G. Tuck, Kellie L. Key, Trevor L. G. Fenalti, Gustavo Pike, Robert N. Rosado, Carlos J. Wong, Anders S. M. Buckle, Ashley M. Law, Ruby H. P. Whisstock, James C. Bioscience Reports Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates Cell Biology Molecular Biology Biochemistry Biophysics |
| author_sort |
langendorf, christopher g. |
| spelling |
Langendorf, Christopher G. Tuck, Kellie L. Key, Trevor L. G. Fenalti, Gustavo Pike, Robert N. Rosado, Carlos J. Wong, Anders S. M. Buckle, Ashley M. Law, Ruby H. P. Whisstock, James C. 0144-8463 1573-4935 Portland Press Ltd. Cell Biology Molecular Biology Biochemistry Biophysics http://dx.doi.org/10.1042/bsr20120111 <jats:p>Imbalances in GABA (γ-aminobutyric acid) homoeostasis underlie psychiatric and movement disorders. The ability of the 65 kDa isoform of GAD (glutamic acid decarboxylase), GAD65, to control synaptic GABA levels is influenced through its capacity to auto-inactivate. In contrast, the GAD67 isoform is constitutively active. Previous structural insights suggest that flexibility in the GAD65 catalytic loop drives enzyme inactivation. To test this idea, we constructed a panel of GAD65/67 chimaeras and compared the ability of these molecules to auto-inactivate. Together, our data reveal the important finding that the C-terminal domain of GAD plays a key role in controlling GAD65 auto-inactivation. In support of these findings, we determined the X-ray crystal structure of a GAD65/67 chimaera that reveals that the conformation of the catalytic loop is intimately linked to the C-terminal domain.</jats:p> Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates Bioscience Reports |
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| title |
Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| title_unstemmed |
Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| title_full |
Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| title_fullStr |
Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| title_full_unstemmed |
Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| title_short |
Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| title_sort |
structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| topic |
Cell Biology Molecular Biology Biochemistry Biophysics |
| url |
http://dx.doi.org/10.1042/bsr20120111 |
| publishDate |
2013 |
| physical |
|
| description |
<jats:p>Imbalances in GABA (γ-aminobutyric acid) homoeostasis underlie psychiatric and movement disorders. The ability of the 65 kDa isoform of GAD (glutamic acid decarboxylase), GAD65, to control synaptic GABA levels is influenced through its capacity to auto-inactivate. In contrast, the GAD67 isoform is constitutively active. Previous structural insights suggest that flexibility in the GAD65 catalytic loop drives enzyme inactivation. To test this idea, we constructed a panel of GAD65/67 chimaeras and compared the ability of these molecules to auto-inactivate. Together, our data reveal the important finding that the C-terminal domain of GAD plays a key role in controlling GAD65 auto-inactivation. In support of these findings, we determined the X-ray crystal structure of a GAD65/67 chimaera that reveals that the conformation of the catalytic loop is intimately linked to the C-terminal domain.</jats:p> |
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| author | Langendorf, Christopher G., Tuck, Kellie L., Key, Trevor L. G., Fenalti, Gustavo, Pike, Robert N., Rosado, Carlos J., Wong, Anders S. M., Buckle, Ashley M., Law, Ruby H. P., Whisstock, James C. |
| author_facet | Langendorf, Christopher G., Tuck, Kellie L., Key, Trevor L. G., Fenalti, Gustavo, Pike, Robert N., Rosado, Carlos J., Wong, Anders S. M., Buckle, Ashley M., Law, Ruby H. P., Whisstock, James C., Langendorf, Christopher G., Tuck, Kellie L., Key, Trevor L. G., Fenalti, Gustavo, Pike, Robert N., Rosado, Carlos J., Wong, Anders S. M., Buckle, Ashley M., Law, Ruby H. P., Whisstock, James C. |
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| description | <jats:p>Imbalances in GABA (γ-aminobutyric acid) homoeostasis underlie psychiatric and movement disorders. The ability of the 65 kDa isoform of GAD (glutamic acid decarboxylase), GAD65, to control synaptic GABA levels is influenced through its capacity to auto-inactivate. In contrast, the GAD67 isoform is constitutively active. Previous structural insights suggest that flexibility in the GAD65 catalytic loop drives enzyme inactivation. To test this idea, we constructed a panel of GAD65/67 chimaeras and compared the ability of these molecules to auto-inactivate. Together, our data reveal the important finding that the C-terminal domain of GAD plays a key role in controlling GAD65 auto-inactivation. In support of these findings, we determined the X-ray crystal structure of a GAD65/67 chimaera that reveals that the conformation of the catalytic loop is intimately linked to the C-terminal domain.</jats:p> |
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| spelling | Langendorf, Christopher G. Tuck, Kellie L. Key, Trevor L. G. Fenalti, Gustavo Pike, Robert N. Rosado, Carlos J. Wong, Anders S. M. Buckle, Ashley M. Law, Ruby H. P. Whisstock, James C. 0144-8463 1573-4935 Portland Press Ltd. Cell Biology Molecular Biology Biochemistry Biophysics http://dx.doi.org/10.1042/bsr20120111 <jats:p>Imbalances in GABA (γ-aminobutyric acid) homoeostasis underlie psychiatric and movement disorders. The ability of the 65 kDa isoform of GAD (glutamic acid decarboxylase), GAD65, to control synaptic GABA levels is influenced through its capacity to auto-inactivate. In contrast, the GAD67 isoform is constitutively active. Previous structural insights suggest that flexibility in the GAD65 catalytic loop drives enzyme inactivation. To test this idea, we constructed a panel of GAD65/67 chimaeras and compared the ability of these molecules to auto-inactivate. Together, our data reveal the important finding that the C-terminal domain of GAD plays a key role in controlling GAD65 auto-inactivation. In support of these findings, we determined the X-ray crystal structure of a GAD65/67 chimaera that reveals that the conformation of the catalytic loop is intimately linked to the C-terminal domain.</jats:p> Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates Bioscience Reports |
| spellingShingle | Langendorf, Christopher G., Tuck, Kellie L., Key, Trevor L. G., Fenalti, Gustavo, Pike, Robert N., Rosado, Carlos J., Wong, Anders S. M., Buckle, Ashley M., Law, Ruby H. P., Whisstock, James C., Bioscience Reports, Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates, Cell Biology, Molecular Biology, Biochemistry, Biophysics |
| title | Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| title_full | Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| title_fullStr | Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| title_full_unstemmed | Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| title_short | Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| title_sort | structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| title_unstemmed | Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates |
| topic | Cell Biology, Molecular Biology, Biochemistry, Biophysics |
| url | http://dx.doi.org/10.1042/bsr20120111 |