PMID: 9891078

Zhou Y, Gottesman MM, Pastan I
Studies of human MDR1-MDR2 chimeras demonstrate the functional exchangeability of a major transmembrane segment of the multidrug transporter and phosphatidylcholine flippase.
Mol Cell Biol. 1999 Feb;19(2):1450-9., [PubMed]
Sentences
No. Mutations Sentence Comment
49 ABCB1 p.Gln330Asn
X
ABCB1 p.Gln330Asn 9891078:49:45
status: NEW
view ABCB1 p.Gln330Asn details
ABCB1 p.Leu332Met
X
ABCB1 p.Leu332Met 9891078:49:63
status: NEW
view ABCB1 p.Leu332Met details
ABCB1 p.Val331Ala
X
ABCB1 p.Val331Ala 9891078:49:52
status: NEW
view ABCB1 p.Val331Ala details
MDR1NAM was created by introducing mutations Q330N, V331A, and L332M into MDR1 by PCR mutagenesis. Login to comment
169 ABCB1 p.Gln330Asn
X
ABCB1 p.Gln330Asn 9891078:169:112
status: NEW
view ABCB1 p.Gln330Asn details
ABCB1 p.Leu332Met
X
ABCB1 p.Leu332Met 9891078:169:130
status: NEW
view ABCB1 p.Leu332Met details
ABCB1 p.Val331Ala
X
ABCB1 p.Val331Ala 9891078:169:119
status: NEW
view ABCB1 p.Val331Ala details
To confirm the significance of Q330, V331, and L332 in TM6, we generated a MDR1 mutant containing the mutations Q330N, V331A, and L332M. Login to comment
226 ABCB1 p.Gln330Asn
X
ABCB1 p.Gln330Asn 9891078:226:30
status: NEW
view ABCB1 p.Gln330Asn details
ABCB1 p.Leu332Met
X
ABCB1 p.Leu332Met 9891078:226:48
status: NEW
view ABCB1 p.Leu332Met details
ABCB1 p.Val331Ala
X
ABCB1 p.Val331Ala 9891078:226:37
status: NEW
view ABCB1 p.Val331Ala details
One is that the substitutions Q330N, V331A, and L332M in MDR1 significantly decreased overall MDR1 multidrug transporter activity. Login to comment
241 ABCB1 p.Gln330Asn
X
ABCB1 p.Gln330Asn 9891078:241:26
status: NEW
view ABCB1 p.Gln330Asn details
ABCB1 p.Leu332Met
X
ABCB1 p.Leu332Met 9891078:241:44
status: NEW
view ABCB1 p.Leu332Met details
ABCB1 p.Val331Ala
X
ABCB1 p.Val331Ala 9891078:241:33
status: NEW
view ABCB1 p.Val331Ala details
Thus, the triple mutation Q330N, V331A, and L332M appeared to have a synergistic effect. Login to comment
262 ABCB1 p.Gln330Asn
X
ABCB1 p.Gln330Asn 9891078:262:176
status: NEW
view ABCB1 p.Gln330Asn details
ABCB1 p.Leu332Met
X
ABCB1 p.Leu332Met 9891078:262:194
status: NEW
view ABCB1 p.Leu332Met details
ABCB1 p.Val331Ala
X
ABCB1 p.Val331Ala 9891078:262:183
status: NEW
view ABCB1 p.Val331Ala details
Since the UIC2 epitope depends on a particular P-gp conformation (24), the decreased level of UIC2 recognition may indicate a conformational change in MDR1 caused by mutations Q330N, V331A, and L332M. Login to comment