6DHK

Bovine glutamate dehydrogenase complexed with ADP

6DHK の概要

• エントリーDOI: 10.2210/pdb6dhk/pdb
• 分子名称: Glutamate dehydrogenase 1, mitochondrial, ADENOSINE-5'-DIPHOSPHATE (2 entities in total)
• 機能のキーワード: dehydrogenase, glutamate, adp, oxidoreductase
• 由来する生物種: Bos taurus (Bovine)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 666658.19

構造登録者

Smith, T.J. (登録日: 2018-05-20, 公開日: 2018-07-25, 最終更新日: 2024-03-13)

主引用文献

Banerjee, S.,Schmidt, T.,Fang, J.,Stanley, C.A.,Smith, T.J.
Structural studies on ADP activation of mammalian glutamate dehydrogenase and the evolution of regulation.
Biochemistry, 42:3446-3456, 2003

PubMed Abstract: Glutamate dehydrogenase (GDH) is found in all organisms and catalyzes the reversible oxidative deamination of L-glutamate to 2-oxoglutarate. Unlike GDH from bacteria, mammalian GDH exhibits negative cooperativity with respect to coenzyme, activation by ADP, and inhibition by GTP. Presented here are the structures of apo bovine GDH, bovine GDH complexed with ADP, and the R463A mutant form of human GDH (huGDH) that is insensitive to ADP activation. In the absence of active site ligands, the catalytic cleft is in the open conformation, and the hexamers form long polymers in the crystal cell with more interactions than found in the abortive complex crystals. This is consistent with the fact that ADP promotes aggregation in solution. ADP is shown to bind to the second, inhibitory, NADH site yet causes activation. The beta-phosphates of the bound ADP interact with R459 (R463 in huGDH) on the pivot helix. The structure of the ADP-resistant, R463A mutant of human GDH is identical to native GDH with the exception of the truncated side chain on the pivot helix. Together, these results strongly suggest that ADP activates by facilitating the opening of the catalytic cleft. From alignment of GDH from various sources, it is likely that the antenna evolved in the protista prior to the formation of purine regulatory sites. This suggests that there was some selective advantage of the antenna itself and that animals evolved new functions for GDH through the addition of allosteric regulation.

PubMed: 12653548
DOI: 10.1021/bi0206917

実験手法

X-RAY DIFFRACTION (3.5 Å)