Structural and biochemical evidence that ATP inhibits the cancer biomarker human aldehyde dehydrogenase 1A3.

ABSTRACT: Human aldehyde dehydrogenase (ALDH) participates in the oxidative stress response and retinoid metabolism, being involved in several diseases, including cancer, diabetes and obesity. The ALDH1A3 isoform has recently elicited wide interest because of its potential use as a cancer stem cell biomarker and drug target. We report high-resolution three-dimensional ALDH1A3 structures for the apo-enzyme, the NAD⁺ complex and a binary complex with ATP. Each subunit of the ALDH1A3-ATP complex contains one ATP molecule bound to the adenosine-binding pocket of the cofactor-binding site. The ATP complex also shows a molecule, putatively identified as a polyethylene glycol aldehyde, covalently bound to the active-site cysteine. This mimics the thioacyl-enzyme catalytic intermediate, which is

SUBMITTER: Castellvi A 

PROVIDER: S-EPMC9007972 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature