2okj: Difference between revisions

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==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.

==Disease==

Known diseases associated with this structure: Cerebral palsy, spastic, symmetric, autosomal recessive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605363 605363]]

==About this Structure==

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[[Category: Homo sapiens]]

[[Category: Single protein]]

[[Category: Buckle, A.M.]]

[[Category: Buckle, A M.]]

[[Category: Fenalti, G.]]

[[Category: Law, R.H.P.]]

[[Category: Law, R H.P.]]

[[Category: Whisstock, J.C.]]

[[Category: Whisstock, J C.]]

[[Category: ABU]]

[[Category: PLZ]]

[[Category: plp-dependent decarboxylase]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Jan 23 15~~:32:26 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:19:29 2008''

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@@ Line 4: / Line 4: @@
 ==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.
+==Disease==
+Known diseases associated with this structure: Cerebral palsy, spastic, symmetric, autosomal recessive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605363 605363]]
 ==About this Structure==
@@ Line 14: / Line 17: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Buckle, A.M.]]
+[[Category: Buckle, A M.]]
 [[Category: Fenalti, G.]]
-[[Category: Law, R.H.P.]]
+[[Category: Law, R H.P.]]
-[[Category: Whisstock, J.C.]]
+[[Category: Whisstock, J C.]]
 [[Category: ABU]]
 [[Category: PLZ]]
 [[Category: plp-dependent decarboxylase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:32:26 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:19:29 2008''