Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT1)–5'-nucleotidase (CD73) protein–protein interface (MGAT1-CD73 PPI)

The MGAT1–CD73 protein–protein interface is a critical regulatory site where the Golgi-resident enzyme Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (MGAT1; UniProt P26374) interacts with the 5'-nucleotidase (CD73; UniProt P21589). This interaction is essential for the N-glycosylation of CD73, a post-translational modification that ensures its proper folding, membrane trafficking, and enzymatic activity (Zhang et al., 2023, Nature Communications). CD73 is a key immunosuppressive enzyme in the tumor microenvironment that converts extracellular AMP into adenosine, which subsequently inhibits anti-tumor immune responses by binding to A2A receptors on T cells and NK cells. In various malignancies, such as triple-negative breast cancer and lung adenocarcinoma, the MGAT1-mediated glycosylation of CD73 is upregulated, promoting immune evasion and resistance to therapy (Zhang et al., 2023). Targeting this specific interface aims to disrupt the maturation of CD73, thereby reducing adenosine production and restoring immune surveillance. While no clinical drugs currently target this interface, it represents a novel therapeutic strategy to selectively inhibit CD73 function without the limitations of direct active-site inhibitors.

Other names

MGAT1-CD73 interactionMGAT1-mediated CD73 glycosylationMGAT1-NT5E interfaceGlcNAc-T I-CD73 interaction

Inhibition of the physical protein-protein interaction between MGAT1 and CD73 to prevent the N-glycosylation-dependent maturation, stability, and enzymatic activation of CD73.