Virtuelle (Nano) Welten: PDB Molecule of the Month 45: Estrogen Receptor

Estrogen and Cancer

Estrogen gives cells permission to grow when appropriate. This is essential during puberty, but also necessary in adult life. For instance, estrogen is important in bone growth, and low levels of estrogens can lead to osteoporosis. But in the case of cancer, estrogen can enhance unnatural growth and make the disease worse. The drug tamoxifen is used to treat cancer by blocking the action of estrogen. Tamoxifen is a small drug that mimics the shape of estrogen and binds tightly to the estrogen receptor. When it binds, it changes the shape of a signaling loop on the surface the receptor, colored green here. The upper structure shown here, from PDB entry 1qku, has estradiol bound (estradiol is not seen in the picture, because it is bound under the loop). The compact conformation of this loop forms part of the activation signal that will stimulate normal growth. The lower structure, from PDB entry 3ert, has the drug bound. Since the drug is larger than the hormone, it forces the activation loop out into an inactive conformation, blocking the signal to grow.