6QAK

Structure of human ALDH9 in P21212 space group

6QAK の概要

• エントリーDOI: 10.2210/pdb6qak/pdb
• 分子名称: 4-trimethylaminobutyraldehyde dehydrogenase, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: aldehyde dehydrogenase, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 443864.91

構造登録者

Morera, S.,Vigouroux, A.,Kopecny, D. (登録日: 2018-12-19, 公開日: 2019-04-10, 最終更新日: 2024-01-24)

主引用文献

Koncitikova, R.,Vigouroux, A.,Kopecna, M.,Sebela, M.,Morera, S.,Kopecny, D.
Kinetic and structural analysis of human ALDH9A1.
Biosci.Rep., 39:-, 2019

PubMed Abstract: Aldehyde dehydrogenases (ALDHs) constitute a superfamily of NAD(P)-dependent enzymes, which detoxify aldehydes produced in various metabolic pathways to the corresponding carboxylic acids. Among the 19 human ALDHs, the cytosolic ALDH9A1 has so far never been fully enzymatically characterized and its structure is still unknown. Here, we report complete molecular and kinetic properties of human ALDH9A1 as well as three crystal forms at 2.3, 2.9, and 2.5 Å resolution. We show that ALDH9A1 exhibits wide substrate specificity to aminoaldehydes, aliphatic and aromatic aldehydes with a clear preference for -trimethylaminobutyraldehyde (TMABAL). The structure of ALDH9A1 reveals that the enzyme assembles as a tetramer. Each ALDH monomer displays a typical ALDHs fold composed of an oligomerization domain, a coenzyme domain, a catalytic domain, and an inter-domain linker highly conserved in amino-acid sequence and folding. Nonetheless, structural comparison reveals a position and a fold of the inter-domain linker of ALDH9A1 never observed in any other ALDH so far. This unique difference is not compatible with the presence of a bound substrate and a large conformational rearrangement of the linker up to 30 Å has to occur to allow the access of the substrate channel. Moreover, the αβE region consisting of an α-helix and a β-strand of the coenzyme domain at the dimer interface are disordered, likely due to the loss of interactions with the inter-domain linker, which leads to incomplete β-nicotinamide adenine dinucleotide (NAD) binding pocket.

PubMed: 30914451
DOI: 10.1042/BSR20190558

実験手法

X-RAY DIFFRACTION (2.5 Å)