2okj: Difference between revisions
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|PDB= 2okj |SIZE=350|CAPTION= <scene name='initialview01'>2okj</scene>, resolution 2.300Å | |PDB= 2okj |SIZE=350|CAPTION= <scene name='initialview01'>2okj</scene>, resolution 2.300Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=ABU:GAMMA-AMINO-BUTANOIC+ACID'>ABU</scene> | |LIGAND= <scene name='pdbligand=ABU:GAMMA-AMINO-BUTANOIC+ACID'>ABU</scene>, <scene name='pdbligand=LLP:2-LYSINE(3-HYDROXY-2-METHYL-5-PHOSPHONOOXYMETHYL-PYRIDIN-4-YLMETHANE)'>LLP</scene>, <scene name='pdbligand=PLZ:4-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]BUTANOIC+ACID'>PLZ</scene> | ||
|ACTIVITY= [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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= GAD1, GAD, GAD67 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= GAD1, GAD, GAD67 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2okk|2OKK]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2okj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2okj OCA], [http://www.ebi.ac.uk/pdbsum/2okj PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2okj RCSB]</span> | |||
}} | }} | ||
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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== | ||
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[[Category: Law, R H.P.]] | [[Category: Law, R H.P.]] | ||
[[Category: Whisstock, J C.]] | [[Category: Whisstock, J C.]] | ||
[[Category: plp-dependent decarboxylase]] | [[Category: plp-dependent decarboxylase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:19:09 2008'' | ||
