2OKK

The X-ray crystal structure of the 65kDa isoform of Glutamic Acid Decarboxylase (GAD65)

2OKK の概要

• エントリーDOI: 10.2210/pdb2okk/pdb
• 関連するPDBエントリー: 2OKJ
• 分子名称: Glutamate decarboxylase 2, GAMMA-AMINO-BUTANOIC ACID, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: plp-dependent decarboxylase, lyase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytosol: Q05329
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57080.66

構造登録者

Buckle, A.M.,Fenalti, G.,Law, R.H.P.,Whisstock, J.C. (登録日: 2007-01-17, 公開日: 2007-03-27, 最終更新日: 2023-11-15)

主引用文献

Fenalti, G.,Law, R.H.,Buckle, A.M.,Langendorf, C.,Tuck, K.,Rosado, C.J.,Faux, N.G.,Mahmood, K.,Hampe, C.S.,Banga, J.P.,Wilce, M.,Schmidberger, J.,Rossjohn, J.,El-Kabbani, O.,Pike, R.N.,Smith, A.I.,Mackay, I.R.,Rowley, M.J.,Whisstock, J.C.
GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop.
Nat.Struct.Mol.Biol., 14:280-286, 2007

PubMed Abstract: 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.

PubMed: 17384644
DOI: 10.1038/nsmb1228

実験手法

X-RAY DIFFRACTION (2.3 Å)