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	<scene name='43/437742/2yxj_glu/2'>two negatively charged residues</scene> Glu96 and Glu129.		<scene name='43/437742/2yxj_glu/2'>two negatively charged residues</scene> Glu96 and Glu129.
	Two <scene name='43/437742/2yxj_hydrophobic/1'>hydrophobic patches</scene> which include Phe191 Val141 and		Two <scene name='43/437742/2yxj_hydrophobic/1'>hydrophobic patches</scene> which include Phe191 Val141 and
-	Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. one can look at the <scene name='43/437742/2yxj_space_fill_color_charged/2'>Overall</scene> picture 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/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.
	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.

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Revision as of 19:37, 28 August 2013

spinqualitylabelsall models Bcl-Xl and ABT737 from PDB-ID 2yxj Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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) ,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. A look at the 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.