Analysis of the Properties of the N-Terminal Nucleotide-Binding Domain of Human P-Glycoprotein†

Biochemistry ◽  
2000 ◽  
Vol 39 (18) ◽  
pp. 5518-5526 ◽  
Author(s):  
Catherine L. Booth ◽  
Lukasz Pulaski ◽  
Michael M. Gottesman ◽  
Ira Pastan
Keyword(s):  
Nucleotide Binding ◽  
Binding Domain ◽  
Nucleotide Binding Domain ◽  
P Glycoprotein ◽  
Terminal Nucleotide

scholarly journals Recombinant N-terminal Nucleotide-binding Domain from Mouse P-glycoprotein

1996 ◽  
Vol 271 (20) ◽  
pp. 11652-11658 ◽  
Author(s):  
Guila Dayan ◽  
Hélène Baubichon-Cortay ◽  
Jean-Michel Jault ◽  
Jean-Claude Cortay ◽  
Gilbert Deléage ◽  
...  
Keyword(s):  
Nucleotide Binding ◽  
Binding Domain ◽  
Nucleotide Binding Domain ◽  
P Glycoprotein ◽  
Terminal Nucleotide

scholarly journals Mutations Define Cross-talk between the N-terminal Nucleotide-binding Domain and Transmembrane Helix-2 of the Yeast Multidrug Transporter Pdr5

2008 ◽  
Vol 283 (50) ◽  
pp. 35010-35022 ◽  
Author(s):  
Zuben E. Sauna ◽  
Sherry Supernavage Bohn ◽  
Robert Rutledge ◽  
Michael P. Dougherty ◽  
Susan Cronin ◽  
...  
Keyword(s):  
Cross Talk ◽  
Transmembrane Helix ◽  
Nucleotide Binding ◽  
Binding Domain ◽  
Multidrug Transporter ◽  
Nucleotide Binding Domain ◽  
Terminal Nucleotide

scholarly journals High-Affinity Binding of Silybin Derivatives to the Nucleotide-Binding Domain of a Leishmania tropicaP-Glycoprotein-Like Transporter and Chemosensitization of a Multidrug-Resistant Parasite to Daunomycin

2001 ◽  
Vol 45 (2) ◽  
pp. 439-446 ◽  
Author(s):  
José M. Pérez-Victoria ◽  
F. Javier Pérez-Victoria ◽  
Gwenaëlle Conseil ◽  
Mathias Maitrejean ◽  
Gilles Comte ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Rational Design ◽  
Nucleotide Binding ◽  
Multidrug Resistant ◽  
Binding Domain ◽  
Nucleotide Binding Domain ◽  
P Glycoprotein ◽  
Vitro Binding ◽  
Cytosolic Domains

ABSTRACT In order to overcome the multidrug resistance mediated by P-glycoprotein-like transporters in Leishmania spp., we have studied the effects produced by derivatives of the flavanolignan silybin and related compounds lacking the monolignol unit on (i) the affinity of binding to a recombinant C-terminal nucleotide-binding domain of the L. tropica P-glycoprotein-like transporter and (ii) the sensitization to daunomycin on promastigote forms of a multidrug-resistant L. tropica line overexpressing the transporter. Oxidation of the flavanonol silybin to the corresponding flavonol dehydrosilybin, the presence of the monolignol unit, and the addition of a hydrophobic substituent such as dimethylallyl, especially at position 8 of ring A, considerably increased the binding affinity. The in vitro binding affinity of these compounds for the recombinant cytosolic domain correlated with their modulation of drug resistance phenotype. In particular, 8-(3,3-dimethylallyl)-dehydrosilybin effectively sensitized multidrug-resistant Leishmania spp. to daunomycin. The cytosolic domains are therefore attractive targets for the rational design of inhibitors against P-glycoprotein-like transporters.

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