Cryo-EM structure and regulation of human NAD kinase.

ABSTRACT: Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a crucial reducing cofactor for reductive biosynthesis and protection from oxidative stress. To fulfill their heightened anabolic and reductive power demands, cancer cells must boost their NADPH production. Progrowth and mitogenic protein kinases promote the activity of cytosolic NAD kinase (NADK), which produces NADP⁺, a limiting NADPH precursor. However, the molecular architecture and mechanistic regulation of human NADK remain undescribed. Here, we report the cryo-electron microscopy structure of human NADK, both in its apo-form and in complex with its substrate NAD⁺ (nicotinamide adenine dinucleotide), revealing a tetrameric organization with distinct structural features. We discover that the amino (N)

SUBMITTER: Praharaj PP 

PROVIDER: S-EPMC11759006 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature