1O01

Human mitochondrial aldehyde dehydrogenase complexed with crotonaldehyde, NAD(H) and Mg2+

1O01 の概要

• エントリーDOI: 10.2210/pdb1o01/pdb
• 関連するPDBエントリー: 1A4Z 1AG8 1CW3 1NZW 1NZX 1NZZ 1O00 1O02 1O04 1O05
• 分子名称: Aldehyde dehydrogenase, MAGNESIUM ION, SODIUM ION, ... (8 entities in total)
• 機能のキーワード: aldh, nad, nadh, isomerization, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion matrix: P05091
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 443072.44

構造登録者

Perez-Miller, S.J.,Hurley, T.D. (登録日: 2003-02-20, 公開日: 2003-06-24, 最終更新日: 2023-08-16)

主引用文献

Perez-Miller, S.J.,Hurley, T.D.
Coenzyme isomerization is integral to catalysis in aldehyde dehydrogenase
Biochemistry, 42:7100-7109, 2003

PubMed Abstract: Crystal structures of many enzymes in the aldehyde dehydrogenase superfamily determined in the presence of bound NAD(P)(+) have exhibited conformational flexibility for the nicotinamide half of the cofactor. This has been hypothesized to be important in catalysis because one conformation would block the second half of the reaction, but no firm evidence has been put forth which shows whether the oxidized and reduced cofactors preferentially occupy the two observed conformations. We present here two structures of the wild type and two structures of a Cys302Ser mutant of human mitochondrial aldehyde dehydrogenase in binary complexes with NAD(+) and NADH. These structures, including the Cys302Ser mutant in complex with NAD(+) at 1.4 A resolution and the wild-type enzyme in complex with NADH at 1.9 A resolution, provide strong evidence that bound NAD(+) prefers an extended conformation ideal for hydride transfer and bound NADH prefers a contracted conformation ideal for acyl-enzyme hydrolysis. Unique interactions between the cofactor and the Rossmann fold make isomerization possible while allowing the remainder of the active site complex to remain intact. In addition, these structures clarify the role of magnesium in activating the human class 2 enzyme. Our data suggest that the presence of magnesium may lead to selection of particular conformations and speed isomerization of the reduced cofactor following hydride transfer.

PubMed: 12795606
DOI: 10.1021/bi034182w

実験手法

X-RAY DIFFRACTION (2.15 Å)