Immunosuppressant drug (FK506) binding protein
Homo sapiens (human)
Sometimes the only way to cure a disease is by transplantation of body organs like the heart or the liver. When such an organ is transferred from one person, the donor, to another person, the recipient, the recipient's immune system treats the organ as foreign. The patient who receives a new organ, thus has not only to deal with the original disease, but in addition with the, potentially very vigorous and swift, response of the immune system. There are several ways to deal with this problem and one of them is called immunosuppression. This technique, as the name says, suppresses the normal response of the immune system. One has to do this carefully, because the patient's body is weak, thus more susceptible to infections and therefore actually more in need of a working immune system rather than a disabled one. Immunophilins are a class a proteins that are involved in the immune response pathway and a potential target for immunosuppressant drugs. They work by forming complexes with other proteins and subsequently blocking the process of signal transduction in T cells. In this way they interfere with normal immune system reaction. A very potent drug was discovered in fungi by the Japanese company Fujisawa. It is very efficient, but also toxic, leading to many side-effects and one would therefore find substitutes for it that are less toxic to the body. The drug is known by the acronym FK506 and it binds to a protein called FKBP.
The structure shown here is the complex of the protein, FKBP, with FK506. Studying the structure allows one to draw conclusions which parts of the drug interact with which parts of the protein. This information can then be used to design new drugs, that bind to FKBP as well or maybe even better than FK506, and at the same time are less toxic to the body. The most important discovery resulting from this study was that the protein itself changes little when FK506 binds, but that FK506 changes its shape significantly when binding to FKBP.
Protein Data Bank (PDB)
author: Arno Paehler