1GZ4

molecular mechanism of the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate

1GZ4 の概要

• エントリーDOI: 10.2210/pdb1gz4/pdb
• 関連するPDBエントリー: 1DO8 1EFK 1EFL 1GZ3 1QR6
• 分子名称: NAD-DEPENDENT MALIC ENZYME, ADENOSINE-5'-TRIPHOSPHATE, TARTRONATE, ... (6 entities in total)
• 機能のキーワード: allosteric regulation, energy metabolism, kinetics, oxidoreductase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Mitochondrion matrix: P23368
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 255424.29

構造登録者

Yang, Z.,Lanks, C.W.,Tong, L. (登録日: 2002-05-15, 公開日: 2002-07-25, 最終更新日: 2024-11-13)

主引用文献

Yang, Z.,Lanks, C.W.,Tong, L.
Molecular Mechanism for the Regulation of Human Mitochondrial Nad(P)(+)-Dependent Malic Enzyme by ATP and Fumarate
Structure, 10:951-, 2002

PubMed Abstract: The regulation of human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD-ME) by ATP and fumarate may be crucial for the metabolism of glutamine for energy production in rapidly proliferating tissues and tumors. Here we report the crystal structure at 2.2 A resolution of m-NAD-ME in complex with ATP, Mn2+, tartronate, and fumarate. Our structural, kinetic, and mutagenesis studies reveal unexpectedly that ATP is an active-site inhibitor of the enzyme, despite the presence of an exo binding site. The structure also reveals the allosteric binding site for fumarate in the dimer interface. Mutations in this binding site abolished the activating effects of fumarate. Comparison to the structure in the absence of fumarate indicates a possible molecular mechanism for the allosteric function of this compound.

PubMed: 12121650
DOI: 10.1016/S0969-2126(02)00788-8

実験手法

X-RAY DIFFRACTION (2.2 Å)