Sandbox Mati: Difference between revisions
Mati Cohen (talk | contribs) No edit summary |
Mati Cohen (talk | contribs) No edit summary |
||
| Line 2: | Line 2: | ||
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene=''>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,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. | <StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene=''>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,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 [[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 [[1bxl]]. | The PDB file [[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 [[1bxl]]. | ||
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/ | Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/9'>two positively charged residues</scene> Arg 100 and Arg 139. | ||
<scene name='43/437742/2yxj_glu/7'>two negatively charged residues</scene> Glu96 and Glu129. | <scene name='43/437742/2yxj_glu/7'>two negatively charged residues</scene> Glu96 and Glu129. | ||
Two <scene name='43/437742/2yxj_hyd/ | Two <scene name='43/437742/2yxj_hyd/4'>hydrophobic patches</scene> which include Phe191 Val141 and | ||
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "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. | Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "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. | 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. | ||