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<~~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~~' /> 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.

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==Symmetry in the Bcl-Xl interface==

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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].

+

<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.

-

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.

+

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]].

-

<scene name='43/437742/2yxj_glu/2'>two negatively charged residues</scene> Glu96 and Glu129.

+

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.

-

Two <scene name='43/437742/~~2yxj_hydrophobic~~/1'>hydrophobic patches</scene> which include Phe191 Val141 and

+

<scene name='43/437742/2yxj_glu/7'>two negatively charged residues</scene> Glu96 and Glu129.

-

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/2'>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.

+

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.

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.

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Symmetry in the Bcl-Xl interface

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-<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' /> 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.
+==Symmetry in the Bcl-Xl interface==
-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].
+<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.
-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.
+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]].
-<scene name='43/437742/2yxj_glu/2'>two negatively charged residues</scene> Glu96 and Glu129.
+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.
-Two <scene name='43/437742/2yxj_hydrophobic/1'>hydrophobic patches</scene> which include Phe191 Val141 and
+<scene name='43/437742/2yxj_glu/7'>two negatively charged residues</scene> Glu96 and Glu129.
-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/2'>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.
+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.
 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.