1PJ2

Crystal structure of human mitochondrial NAD(P)+-dependent malic enzyme in a pentary complex with natural substrate malate, cofactor NADH, Mn++, and allosteric activator fumarate

1PJ2 の概要

• エントリーDOI: 10.2210/pdb1pj2/pdb
• 関連するPDBエントリー: 1PJ3 1PJ4
• 分子名称: NAD-dependent malic enzyme, mitochondrial, (2S)-2-hydroxybutanedioic acid, MANGANESE (II) ION, ... (6 entities in total)
• 機能のキーワード: oxidative decarboxylase, 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: 262116.59

構造登録者

Tao, X.,Yang, Z.,Tong, L. (登録日: 2003-05-30, 公開日: 2003-11-11, 最終更新日: 2024-10-30)

主引用文献

Tao, X.,Yang, Z.,Tong, L.
Crystal structures of substrate complexes of malic enzyme and insights into the catalytic mechanism.
Structure, 11:1141-1150, 2003

PubMed Abstract: Malic enzymes catalyze the oxidative decarboxylation of L-malate to pyruvate and CO(2) with the reduction of the NAD(P)(+) cofactor in the presence of divalent cations. We report the crystal structures at up to 2.1 A resolution of human mitochondrial NAD(P)(+)-dependent malic enzyme in different pentary complexes with the natural substrate malate or pyruvate, the dinucleotide cofactor NAD(+) or NADH, the divalent cation Mn(2+), and the allosteric activator fumarate. Malate is bound deep in the active site, providing two ligands for the cation, and its C4 carboxylate group is out of plane with the C1-C2-C3 atoms, facilitating decarboxylation. The divalent cation is positioned optimally to catalyze the entire reaction. Lys183 is the general base for the oxidation step, extracting the proton from the C2 hydroxyl of malate. Tyr112-Lys183 functions as the general acid-base pair to catalyze the tautomerization of the enolpyruvate product from decarboxylation to pyruvate.

PubMed: 12962632
DOI: 10.1016/S0969-2126(03)00168-0

実験手法

X-RAY DIFFRACTION (2.3 Å)