Crystal structure of human aldehyde dehydrogenase 1A3 complexed with NAD⁺ and retinoic acid.

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 repres

SUBMITTER: Moretti A 

PROVIDER: S-EPMC5069622 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature