5FHZ

Human aldehyde dehydrogenase 1A3 complexed with NAD(+) and retinoic acid

5FHZ の概要

• エントリーDOI: 10.2210/pdb5fhz/pdb
• 分子名称: Aldehyde dehydrogenase family 1 member A3, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, RETINOIC ACID, ... (4 entities in total)
• 機能のキーワード: human, retinaldehyde dehydrogenase, tetramer, product-bound structure, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : P47895
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 472001.36

構造登録者

Moretti, A.,Rizzi, M.,Garavaglia, S. (登録日: 2015-12-22, 公開日: 2016-11-02, 最終更新日: 2024-01-10)

主引用文献

Moretti, A.,Li, J.,Donini, S.,Sobol, R.W.,Rizzi, M.,Garavaglia, S.
Crystal structure of human aldehyde dehydrogenase 1A3 complexed with NAD(+) and retinoic acid.
Sci Rep, 6:35710-35710, 2016

PubMed Abstract: The aldehyde dehydrogenase family 1 member A3 (ALDH1A3) catalyzes the oxidation of retinal to the pleiotropic factor retinoic acid using NAD. The level of ALDHs enzymatic activity has been used as a cancer stem cell marker and seems to correlate with tumour aggressiveness. Elevated ALDH1A3 expression in mesenchymal glioma stem cells highlights the potential of this isozyme as a prognosis marker and drug target. Here we report the first crystal structure of human ALDH1A3 complexed with NAD and the product all-trans retinoic acid (REA). The tetrameric ALDH1A3 folds into a three domain-based architecture highly conserved along the ALDHs family. The structural analysis revealed two different and coupled conformations for NAD and REA that we propose to represent two snapshots along the catalytic cycle. Indeed, the isoprenic moiety of REA points either toward the active site cysteine, or moves away adopting the product release conformation. Although ALDH1A3 shares high sequence identity with other members of the ALDH1A family, our structural analysis revealed few peculiar residues in the 1A3 isozyme active site. Our data provide information into the ALDH1As catalytic process and can be used for the structure-based design of selective inhibitors of potential medical interest.

PubMed: 27759097
DOI: 10.1038/srep35710

実験手法

X-RAY DIFFRACTION (2.9 Å)