Alteration of Substrate Specificity by Mutations at the His61Position in Predicted Transmembrane Domain 1 of Human MDR1/P-Glycoprotein†

Biochemistry ◽  
1997 ◽  
Vol 36 (29) ◽  
pp. 8883-8889 ◽  
Author(s):  
Yoshitomo Taguchi ◽  
Kouichi Kino ◽  
Masaki Morishima ◽  
Tohru Komano ◽  
Susan E. Kane ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Transmembrane Domain ◽  
P Glycoprotein ◽  
Human Mdr1

Amino acid substitutions in the first transmembrane domain (TM1) of P-glycoprotein that alter substrate specificity

FEBS Letters ◽  
1997 ◽  
Vol 413 (1) ◽  
pp. 142-146 ◽  
Author(s):  
Yoshitomo Taguchi ◽  
Masaki Morishima ◽  
Tohru Komano ◽  
Kazumitsu Ueda
Keyword(s):  
Amino Acid ◽  
Substrate Specificity ◽  
Transmembrane Domain ◽  
Amino Acid Substitutions ◽  
P Glycoprotein

Contribution to Substrate Specificity and Transport of Nonconserved Residues in Transmembrane Domain 12 of Human P-Glycoprotein†

Biochemistry ◽  
1998 ◽  
Vol 37 (46) ◽  
pp. 16400-16409 ◽  
Author(s):  
Peter Hafkemeyer ◽  
Saibal Dey ◽  
Suresh V. Ambudkar ◽  
Christine A. Hrycyna ◽  
Ira Pastan ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Transmembrane Domain ◽  
P Glycoprotein

scholarly journals Studies of Human MDR1-MDR2 Chimeras Demonstrate the Functional Exchangeability of a Major Transmembrane Segment of the Multidrug Transporter and Phosphatidylcholine Flippase

1999 ◽  
Vol 19 (2) ◽  
pp. 1450-1459 ◽  
Author(s):  
Yi Zhou ◽  
Michael M. Gottesman ◽  
Ira Pastan
Keyword(s):  
Functional Relationship ◽  
Transmembrane Domain ◽  
Site Directed Mutagenesis ◽  
Multidrug Transporter ◽  
Transmembrane Segment ◽  
Glycoprotein P ◽  
Hydrophobic Compounds ◽  
Functional Differences ◽  
P Glycoprotein ◽  
Human Mdr1

ABSTRACT P-glycoprotein (P-gp), encoded by the MDR1 gene, is a plasma membrane transporter which effluxes a large number of structurally nonrelated hydrophobic compounds. The molecular basis of the broad substrate recognition of P-gp is not well understood. Despite the 78% amino acid sequence identity of the MDR1 andMDR2 transporter, MDR2, which has been identified as a phosphatidylcholine transporter, does not transport most MDR1 substrates. The structural and functional differences between MDR1 and MDR2 provide an opportunity to identify the residues essential for the broad substrate spectrum of MDR1. Using an approach involving exchanging homologous segments of MDR1 and MDR2 and site-directed mutagenesis, we have demonstrated that MDR1 residues Q330, V331, and L332 in transmembrane domain 6 are sufficient to allow an MDR2 backbone in the N-terminal half of P-gp to transport several MDR1 substrates, including bisantrene, colchicine, vinblastine, and rhodamine-123. These studies help define some residues important for multidrug transport and indicate the close functional relationship between the multidrug transporter (MDR1) and phosphatidylcholine flippase (MDR2).

scholarly journals N-glycosylation and deletion mutants of the human MDR1 P-glycoprotein.

1993 ◽  
Vol 268 (10) ◽  
pp. 7474-7481 ◽  
Author(s):  
A.H. Schinkel ◽  
S. Kemp ◽  
M. Dollé ◽  
G. Rudenko ◽  
E. Wagenaar
Keyword(s):  
Deletion Mutants ◽  
P Glycoprotein ◽  
Human Mdr1

scholarly journals Identification of residues in the first cytoplasmic loop of P-glycoprotein involved in the function of chimeric human MDR1-MDR2 transporters.

1992 ◽  
Vol 267 (35) ◽  
pp. 25153-25159
Author(s):  
S.J. Currier ◽  
S.E. Kane ◽  
M.C. Willingham ◽  
C.O. Cardarelli ◽  
I Pastan ◽  
...  
Keyword(s):  
Cytoplasmic Loop ◽  
P Glycoprotein ◽  
Human Mdr1

A new polymorphism (N21D) in the exon 2 of the human MDR1 gene encoding the P-glycoprotein

2000 ◽  
Vol 15 (5) ◽  
pp. 486-486 ◽  
Author(s):  
Xavier Decl�ves ◽  
Sylvie Chevillard ◽  
Charlotte Charpentier ◽  
Philippe Vielh ◽  
Jean-Louis Laplanche
Keyword(s):  
Mdr1 Gene ◽  
Gene Encoding ◽  
Exon 2 ◽  
P Glycoprotein ◽  
Human Mdr1
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