GAPDH heme delivery to Indoleamine 2,3-dioxygenase 1 involves their complex formation and complementary charge pairing at the protein-protein interface.

ABSTRACT: In eukaryotes, the last steps of heme biosynthesis occur in mitochondria and so heme must be transported to reach many heme-dependent proteins that mature and function outside this organelle. Although the enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) has emerged as a key intracellular heme chaperone, how it performs heme deliveries to its numerous clients is poorly understood. It is unknown if handoffs of the GAPDH-bound heme require that it make direct contact with its clients or instead involve GAPDH passing its heme to middlemen proteins to execute the final heme transfers. To address this question, we studied GAPDH heme transfer to the client protein indoleamine 2,3-dioxygenase 1 (IDO1), whose enzyme activity is heme-dependent and regulates mammalian immune responses and canc

SUBMITTER: Biswas P 

PROVIDER: S-EPMC12329532 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature