Sandbox Mati
Bcl-Xl is a member of the Bcl-2 family .
This family consists of pro-apoptotic and anti-apoptotic members. Bcl-Xl (in the image)
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,an anti apoptotic protein, binds pro apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.
The PDB file 2yxjshows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl Kd = 1nM. It binds Bcl-xl in the same position as BAK does as can be seen in 1bxl. Interestingly the interface of Bcl-Xl is almost symmetric. There are Arg 100 and Arg 139. Glu96 and Glu129. Two which include Phe191 Val141 and Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. one can look at the picture that there are hydropobic patches "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it. This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.