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This [[Help:Sandboxes|Sandbox]] page is available for temporary practice work. Nothing in a ''Sandbox'' page is permanent. You may prefer to create your own personal Sandbox page -- see [[Help:Getting Started in Proteopedia|instructions]]. Feel free to add practice content below this paragraph, or delete everything below this paragraph, but please do not delete this paragraph.
==Symmetry in the Bcl-Xl interface==
 
<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]].
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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.
<Structure load='1FJ1' size='500' frame='true' align='right' caption='OspA with Antibody Fab LA-2' scene='Insert optional scene name here' />
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.
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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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Markus Heitzer, Eran Hodis, Michael Patrick, Francis Ayombil, David L. Nelson, Sang Joon Won, Wayne Decatur, Eric Martz, Andrew R. Chandra, Conor Finnegan, Student, Test Account 2, Nicholas Michalakis, Paramjit Singh, Nabil Faridi, Christina Evans, Carolyn Carr, Johanna Spaniol, Pernelle Klein, Andréa Mc Cann, Isaac Nyandwi, Min Gi Choi, Yasuaki Shida, Mati Cohen