2okj: Difference between revisions
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New page: left|200px<br /> <applet load="2okj" size="450" color="white" frame="true" align="right" spinBox="true" caption="2okj, resolution 2.300Å" /> '''The X-ray crystal ... |
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[[Image:2okj.gif|left|200px]]<br /> | [[Image:2okj.gif|left|200px]]<br /><applet load="2okj" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2okj" size=" | |||
caption="2okj, resolution 2.300Å" /> | caption="2okj, resolution 2.300Å" /> | ||
'''The X-ray crystal structure of the 67kDa isoform of Glutamic Acid Decarboxylase (GAD67)'''<br /> | '''The X-ray crystal structure of the 67kDa isoform of Glutamic Acid Decarboxylase (GAD67)'''<br /> | ||
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==Overview== | ==Overview== | ||
Gamma-aminobutyric acid (GABA) is synthesized by two isoforms of the, pyridoxal 5'-phosphate-dependent enzyme glutamic acid decarboxylase (GAD65, and GAD67). GAD67 is constitutively active and is responsible for basal, GABA production. In contrast, GAD65, an autoantigen in type I diabetes, is, transiently activated in response to the demand for extra GABA in, neurotransmission, and cycles between an active holo form and an inactive, apo form. We have determined the crystal structures of N-terminal, truncations of both GAD isoforms. The structure of GAD67 shows a tethered, loop covering the active site, providing a catalytic environment that, sustains GABA production. In contrast, the same catalytic loop is, inherently mobile in GAD65. Kinetic studies suggest that mobility in the, catalytic loop promotes a side reaction that results in cofactor release, and GAD65 autoinactivation. These data reveal the molecular basis for, regulation of GABA homeostasis. | Gamma-aminobutyric acid (GABA) is synthesized by two isoforms of the, pyridoxal 5'-phosphate-dependent enzyme glutamic acid decarboxylase (GAD65, and GAD67). GAD67 is constitutively active and is responsible for basal, GABA production. In contrast, GAD65, an autoantigen in type I diabetes, is, transiently activated in response to the demand for extra GABA in, neurotransmission, and cycles between an active holo form and an inactive, apo form. We have determined the crystal structures of N-terminal, truncations of both GAD isoforms. The structure of GAD67 shows a tethered, loop covering the active site, providing a catalytic environment that, sustains GABA production. In contrast, the same catalytic loop is, inherently mobile in GAD65. Kinetic studies suggest that mobility in the, catalytic loop promotes a side reaction that results in cofactor release, and GAD65 autoinactivation. These data reveal the molecular basis for, regulation of GABA homeostasis. | ||
==About this Structure== | ==About this Structure== | ||
2OKJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ABU and PLZ as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutamate_decarboxylase Glutamate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.15 4.1.1.15] Full crystallographic information is available from [http:// | 2OKJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ABU:'>ABU</scene> and <scene name='pdbligand=PLZ:'>PLZ</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutamate_decarboxylase Glutamate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.15 4.1.1.15] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OKJ OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: plp-dependent decarboxylase]] | [[Category: plp-dependent decarboxylase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:32:26 2008'' | ||
