Sandbox PgpWWC
From Proteopedia
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== Structure == | == Structure == | ||
| - | ABCB1 is located in the cellular membrane, adopting an inward-facing "V-shaped" structure. The entrance of substrate into the structure is argued to occur | + | ABCB1 is located in the cellular membrane, adopting an inward-facing "V-shaped" structure. The entrance of substrate into the structure is argued to occur from a cavity in the lipid bilayer.<ref name="Aller" /> When a substrate binds to the binding site, a conformational change causes a scissor-like action that causes the protein to open to the outside of the cell, releasing the substrate. ATP is then hydrolyzed to re-induce the inward-facing conformation in preparation for the binding of another substrate compound from the bilayer.<ref>Chufan, E. E., Sim, H. M., & Ambudkar, S. V. (2014). Chapter Three – Molecular Basis of the Polyspecificity of P-Glycoprotein (ABCB1): Recent Biochemical and Structural Studies. Advances in Cancer Research, 125, 71-96</ref> This efflux of substrate out of the cell prevents the accumulation of potentially toxic xenobiotics; however, this effective expulsion of a wide variety of substrates caused the multi-drug resistance. |
The polyspecificity of ABCB1 is often attributed to a large internal cavity of ~6,000 Å that can transport up to two compounds simultaneously ranging from sizes of 330-4,000 Da. Three binding sites have been proposed, including the H (Hoescht), R (rhodamine), and the P (prazosin and progesterone) sites.<ref name="Aller" /> | The polyspecificity of ABCB1 is often attributed to a large internal cavity of ~6,000 Å that can transport up to two compounds simultaneously ranging from sizes of 330-4,000 Da. Three binding sites have been proposed, including the H (Hoescht), R (rhodamine), and the P (prazosin and progesterone) sites.<ref name="Aller" /> | ||
== Clinical Relevance == | == Clinical Relevance == | ||
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| - | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 20:42, 23 April 2015
P-glycoprotein (ABCB1)
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References
- ↑ 1.0 1.1 1.2 Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science. 2009 Mar 27;323(5922):1718-22. PMID:19325113 doi:323/5922/1718
- ↑ He L, Liu GQ. Effects of various principles from Chinese herbal medicine on rhodamine123 accumulation in brain capillary endothelial cells. Acta Pharmacol Sin. 2002 Jul;23(7):591-6. PMID:12100750
- ↑ Marchetti S, Mazzanti R, Beijnen JH, Schellens JH. Concise review: Clinical relevance of drug drug and herb drug interactions mediated by the ABC transporter ABCB1 (MDR1, P-glycoprotein). Oncologist. 2007 Aug;12(8):927-41. PMID:17766652 doi:http://dx.doi.org/10.1634/theoncologist.12-8-927
- ↑ Chufan, E. E., Sim, H. M., & Ambudkar, S. V. (2014). Chapter Three – Molecular Basis of the Polyspecificity of P-Glycoprotein (ABCB1): Recent Biochemical and Structural Studies. Advances in Cancer Research, 125, 71-96
