scholarly journals Homology modeling and substrate binding studies of human P-glycoprotein

2017 ◽  
Vol 44 (2) ◽  
pp. 96-107
Author(s):  
Jutarat Pimthon ◽  
Rawinsiwat Dechaanontasup ◽  
Chanapa Ratanapiphop ◽  
Chalanrat Phromprasert
Keyword(s):  
Homology Modeling ◽  
Substrate Binding ◽  
Binding Studies ◽  
P Glycoprotein

Role of Cytochrome P450 in Tulip Bulb Probed by Substrate-Binding Studies

1992 ◽  
Vol 36 (1) ◽  
pp. 27-30 ◽  
Author(s):  
Steven L. Kelly ◽  
Aysegul Topal ◽  
Ian Barnett ◽  
Diane E. Kelly ◽  
George A. F. Hendry
Keyword(s):  
Cytochrome P450 ◽  
Substrate Binding ◽  
Binding Studies ◽  
Tulip Bulb

Homology modeling and binding site assessment of the human P-glycoprotein

2011 ◽  
Vol 3 (3) ◽  
pp. 297-307 ◽  
Author(s):  
Ákos Tarcsay ◽  
György M Keserű
Keyword(s):  
Homology Modeling ◽  
Binding Site ◽  
Site Assessment ◽  
P Glycoprotein

scholarly journals Characterization of the Catalytic Cycle of ATP Hydrolysis by Human P-glycoprotein

2001 ◽  
Vol 276 (15) ◽  
pp. 11653-11661 ◽  
Author(s):  
Zuben E. Sauna ◽  
Suresh V. Ambudkar
Keyword(s):  
Multidrug Resistance ◽  
Functional Outcomes ◽  
Atp Hydrolysis ◽  
Substrate Binding ◽  
Nucleotide Binding ◽  
Catalytic Cycle ◽  
Nucleotide Binding Sites ◽  
P Glycoprotein ◽  
Random Manner

P-glycoprotein (Pgp) is a plasma membrane protein whose overexpression confers multidrug resistance to tumor cells by extruding amphipathic natural product cytotoxic drugs using the energy of ATP. An elucidation of the catalytic cycle of Pgp would help design rational strategies to combat multidrug resistance and to further our understanding of the mechanism of ATP-binding cassette transporters. We have recently reported (Sauna, Z. E., and Ambudkar, S. V. (2000)Proc. Natl. Acad. Sci. U. S. A.97, 2515–2520) that there are two independent ATP hydrolysis events in a single catalytic cycle of Pgp. In this study we exploit the vanadate (Vi)-induced transition state conformation of Pgp (Pgp·ADP·Vi) to address the question of what are the effects of ATP hydrolysis on the nucleotide-binding site. We find that at the end of the first hydrolysis event there is a drastic decrease in the affinity of nucleotide for Pgp coincident with decreased substrate binding. Release of occluded dinucleotide is adequate for the next hydrolysis event to occur but is not sufficient for the recovery of substrate binding. Whereas the two hydrolysis events have different functional outcomesvis à visthe substrate, they show comparablet12for both incorporation and release of nucleotide, and the affinities for [α-32P]8-azido-ATP during Vi-induced trapping are identical. In addition, the incorporation of [α-32P]8-azido-ADP in two ATP sites during both hydrolysis events is also similar. These data demonstrate that during individual hydrolysis events, the ATP sites are recruited in a random manner, and only one site is utilized at any given time because of the conformational change in the catalytic site that drastically reduces the affinity of the second ATP site for nucleotide binding. In aggregate, these findings provide an explanation for the alternate catalysis of ATP hydrolysis and offer a mechanistic framework to elucidate events at both the substrate- and nucleotide-binding sites in the catalytic cycle of Pgp.

Molecular Docking Characterizes Substrate-Binding Sites and Efflux Modulation Mechanisms within P-Glycoprotein.

2013 ◽  
Vol 53 (7) ◽  
pp. 1747-1760 ◽  
Author(s):  
Ricardo J. Ferreira ◽  
Maria-José U. Ferreira ◽  
Daniel J. V. A. dos Santos
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Substrate Binding ◽  
P Glycoprotein ◽  
Substrate Binding Sites

scholarly journals Homology Modeling of P-glycoprotein for Detecting Remote Protein Homologies

2012 ◽  
Vol 38 ◽  
pp. 1778-1782
Author(s):  
Anurag Pal ◽  
Debahuti Mishra ◽  
Shruti Mishra ◽  
Sandeep Kumar Satapathy
Keyword(s):  
Homology Modeling ◽  
P Glycoprotein

Homology modeling and in silico screening of inhibitors for the substrate binding domain of human Siah2: implications for hypoxia-induced cancers

2011 ◽  
Vol 17 (12) ◽  
pp. 3325-3332 ◽  
Author(s):  
Gopalsamy Anupriya ◽  
Kothapalli Roopa ◽  
S. Basappa ◽  
Yap Seng Chong ◽  
Loganath Annamalai
Keyword(s):  
Homology Modeling ◽  
In Silico ◽  
Substrate Binding ◽  
Binding Domain ◽  
In Silico Screening ◽  
Substrate Binding Domain
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