<i><span style="font-size:11.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB">In silico</span></i><span style="font-size:11.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-bidi-font-family: Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US;mso-bidi-language: HI" lang="EN-GB"> <span style="font-size:11.0pt;mso-bidi-font-size:12.0pt; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US; mso-bidi-language:HI" lang="EN-GB">exploration<span style="font-size:11.0pt; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:Mangal;mso-ansi-language:EN-GB;mso-fareast-language:EN-US; mso-bidi-language:HI" lang="EN-GB"> of phenytoin binding site in two catalytic states of human P-glycoprotein models</span></span></span>
NOPR - NISCAIR Online Periodicals Repository
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Title |
In silico exploration of phenytoin binding site in two catalytic states of human P-glycoprotein models
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Creator |
Cleave A, Suneetha Susan
Panda, Roshni Suresh, P K |
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Subject |
P-Glycoprotein
Multidrug resistance Phenytoin Efflux Drug binding site In silico |
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Description |
7-13
P-glycoprotein (P-gp), an ATP-dependant efflux pump transports a wide range of substrates across cellular membranes. Earlier studies have identified drug efflux due to the over-expression of P-gp as one of the causes for the resistance of phenytoin, an anti-epileptic drug (AED). While no clear evidence exists on the specific characteristics of phenytoin association with the human P-gp, this study employed structure-based computational approaches to identify its binding site and the underlying interactions. The identified site was validated with that of rhodamine, a widely accepted reference and an experimental probe. Further, an in silico proof-of-concept for phenytoin interactions and its decreased binding affinity with the closed-state of human P-gp model was provided in comparison with other AEDs. This is the first report to provide insights into the phenytoin binding site and possibly better explain its efflux by P-gp. |
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Date |
2013-02-23T11:18:36Z
2013-02-23T11:18:36Z 2013-02 |
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Type |
Article
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Identifier |
0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/16058 |
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Language |
en_US
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Rights |
CC Attribution-Noncommercial-No Derivative Works 2.5 India
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Publisher |
NISCAIR-CSIR, India
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Source |
IJBB Vol.50(1) [February 2013]
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