Sandbox Mati
From Proteopedia
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| - | Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family] . This family consists of pro-apoptotic and anti-apoptotic members. Bcl-Xl(in the image) <Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> ,an anti apoptotic protein, binds pro apoptotic proteins like BAK and BAD thus | + | Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family] . This family consists of pro-apoptotic and anti-apoptotic members. Bcl-Xl (in the image) <Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> ,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 apoptosis . Therefore these proteins are important targets for the development of new anti-cancer drugs. |
| - | + | The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows 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 [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl]. | |
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/3'>two positively charged residues</scene> Arg 100 and Arg 139. | Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/3'>two positively charged residues</scene> Arg 100 and Arg 139. | ||
<scene name='43/437742/2yxj_glu/2'>two negativly charged residues</scene> Glu 96 and Glu 129. | <scene name='43/437742/2yxj_glu/2'>two negativly charged residues</scene> Glu 96 and Glu 129. | ||
Revision as of 07:10, 28 August 2013
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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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. Glu 96 and Glu 129. Two which include Phe 191 Val 141 and Ala 93 for one, and the other patch includes Phe 146 Val 126 and Leu 108.Now 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 an exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity .
