BCL2 and Venetoclax, an antileukemia drug (6O0K)

sketchfab

Cancer cells exhibit immortality due to their resistance to apoptosis, as they thwart programmed cell death. In patients afflicted with chronic lymphocytic leukemia, a pivotal mediator of cancer cell immortality is BCL-2, a 'pro-survival' protein that blocks the activity of 'pro-apoptotic' proteins such as BAX and BAK. This binding occurs between a complementary groove on the surface of BCL-2 and a helical BCL-2 Homology 3 (BH3) motif found on pro-apoptotic proteins. Venetoclax is one of the first anti-cancer drugs that works by directly blocking a protein-protein interaction. Specifically, venetoclax functions as a BCL-2 antagonist: it binds to the complementary groove on the surface of BCL-2, competitively inhibiting interaction with BH3 motifs. This prevents the cancer cell from evading apoptosis and leads to cell death. This model illustrates the interaction between BCL-2 and venetoclax (PDB: 6O0K) and explores the mechanism by which a specific mutation in BCL-2 enables cancer cells to develop resistance to venetoclax.