Structural and biochemical basis for the inhibition of cell death by APIP, a methionine salvage enzyme

Apaf-1 interacting protein (APIP) inhibits two main types of programmed cell death: apoptosis and pyroptosis. In addition, APIP is a 5-methylthioribulose-1-phosphate dehydratase (MtnB) in the methionine salvage pathway. We verified its enzymatic activity directly through an enzyme assay and determined its high-resolution structure. Furthermore, we explored the relationship between two distinct functions of APIP/MtnB, cell death inhibition and methionine salvage, and determined that it functions as a cell death inhibitor independently of its MtnB enzyme activity for apoptosis, but dependently for caspase-1–induced pyroptosis. Our results provide groundwork for studies of the role of APIP/MtnB in development of cancers and inflammatory diseases.