ABCB1 p.Gly64Arg
[switch to full view]Comments [show]
None has been submitted yet.
PMID: 10331089
[PubMed]
Ambudkar SV et al: "Biochemical, cellular, and pharmacological aspects of the multidrug transporter."
No.
Sentence
Comment
47
Table 1 List of mutations in human, mouse, and hamster P-glycoproteins that affect substrate specificitya aa mutation Region Sourceb Reference H61R, F, K, M, W, Y TM 1 Human MDR1 149, 150 ABC20c G64R TM 1 Human MDR1 150 L65R TM 1 Human MDR1 150 aa78-97 EC 1 Human MDR1 151 Q128Hd TM 2 Mouse mdr3 152 R138H IC 1 Mouse mdr3 152 Q139H, R IC 1 Mouse mdr3 152 Q141V IC 1 Human MDR1 15319, Q145H IC 1 Mouse mdr3 152 E155G, K IC 1 Mouse mdr3 152 F159I IC 1 Mouse mdr3 152 D174G IC 1 Mouse mdr3 152 S176G, P IC 1 Mouse mdr3 152 K177I IC 1 Mouse mdr3 152 N179S IC 1 Mouse mdr3 152 N183S/G185V IC 1 Human MDR1 154 G183D IC 1 Mouse mdr3 152 G185V IC 1 Human MDR1 155-157 G187V IC 1 Human MDR1 153 A192T TM 3 Mouse mdr3 152 F204S EC 2 Mouse mdr3 152 W208G EC 2 Mouse mdr3 152 K209E EC 2 Mouse mdr3 152 L210I TM 4 Mouse mdr3 152 T211P TM 4 Mouse mdr3 152 I214T TM 4 Mouse mdr3 152 P223A TM 4 Human MDR1 158 G288V IC 2 Human MDR1 153 I299M, T319S, L322I, TM 5, EC3, Human MDR1 159 G324K, S351N IC 3 F335A TM 6 Human MDR1 19 F335 TM 6 Human MDR1 160 V338A TM 6 Human MDR1 161 G338A, A339P TM 6 Hamster PGY1 162, 163 A339P TM 6 Hamster PGY1 163 G341V TM 6 Human MDR1 161 K536R, Q N-NBD Human MDR1 164 ERGA → DKGT N-NBD Mouse mdr3 165 aa 522-525 T578C N-NBD Mouse mdr3 165 (Continued) G830V IC 4 Human MDR1 P866A TM 10 Human MDR1 158 F934A TM 11 Mouse mdr3 166 G935A TM 11 Mouse mdr3 166 I936A TM 11 Mouse mdr3 166 F938A TM 11 Mouse mdr3 166 S939A TM 11 Mouse mdr3 166 S939F TM 11 Mouse mdr3 167, 168 S941F TM 11 Mouse mdr1 167, 168 T941A TM 11 Mouse mdr3 166 Q942A TM 11 Mouse mdr3 166 A943G TM 11 Mouse mdr3 166 Y946A TM 11 Mouse mdr3 166 S948A TM 11 Mouse mdr3 166 Y949A TM 11 Mouse mdr3 166 C952A TM 11 Mouse mdr3 166 F953A TM 11 Mouse mdr3 166 F983A TM 12 Human MDR1 169 L975A, V981A, F983A TM 12 Human MDR1 169 M986A, V988A, Q990A, TM 12 Human MDR1 169 V991A V981A, F983A TM 12 Human MDR1 169 L975A, F983A TM 12 Human MDR1 169 L975A, V981A TM 12 Human MDR1 169 F978A TM 12 Human MDR1 19 a aa,amino acid; EC, extracellular loop; IC, intracellular loop; TM,transmembrane domain; NBD, nucleotide binding/utilization domain.
X
ABCB1 p.Gly64Arg 10331089:47:195
status: NEW
PMID: 18596043
[PubMed]
Loo TW et al: "Arginines in the first transmembrane segment promote maturation of a P-glycoprotein processing mutant by hydrogen bond interactions with tyrosines in transmembrane segment 11."
No.
Sentence
Comment
55
For disulfide cross-linking analysis, the cDNA of mutant L339C(TM6)/F728C(TM7) (16) was modified to also encode the G64R, M68R, or V71R mutations.
X
ABCB1 p.Gly64Arg 18596043:55:116
status: NEW104 Mutants G64R and V71R showed maturation efficiencies of FIGURE 1.
X
ABCB1 p.Gly64Arg 18596043:104:8
status: NEW153 Mutant G64R only showed significant rescue with cyclosporin A and rhodamine B.
X
ABCB1 p.Gly64Arg 18596043:153:7
status: NEW156 Because the G64R and V71R changes also promoted maturation of the G251V processing mutant (Fig. 2), we also introduced these mutations into the L339C(TM6)/F728C(TM7) mutant.
X
ABCB1 p.Gly64Arg 18596043:156:12
status: NEW165 TABLE 1 Effects of drug substrates on the maturation of TM1 arginine mutants containing the G251V mutation Mutation (G251V ؉) No drug Cyclosporin A Verapamil Vinblastine Rhodamine None - 111a,c 111 111 11 V52R -a,b 111 111 111 11 V53R 2 - - - - G64R 2 - - - - T55R 2 - - - - L56R 2 - - - - A57R 2 - - - - A58R 2 - - - - I59R 2 - - - - I60R 2 - - - - H61R - 111 1 1 1 G62R 2 - - - - A63R 2 - - - - G64R 1 111 1 1 11 L65R 11 111 11 11 11 P66R 2 1 - - - L67R - 111 111 111 11 M68R 111 111 111 111 111 M69R - 111 - 11 111 L70R - 111 111 111 11 V71R 1 111 111 111 11 F72R 2 1 1 1 1 a Change in the amount of mature (170 kDa) protein in the presence of drug substrate relative to that in the absence of drug substrate.
X
ABCB1 p.Gly64Arg 18596043:165:251
status: NEWX
ABCB1 p.Gly64Arg 18596043:165:403
status: NEW173 Membranes were prepared from HEK 293 cells expressing mutants L339C(TM6)/F728C(TM7), G64R/ L339C(TM6)/F728C(TM7), M68R/ L339C(TM6)/F728C(TM7), and V71R/L339C(TM6)/F728C(TM7).
X
ABCB1 p.Gly64Arg 18596043:173:85
status: NEW181 The G64R/L339C(TM6)/ F728C(TM7) mutant also showed a large reduction in apparent affinity for vinblastine (Ͼ100-fold), whereas the V71R change had little effect.
X
ABCB1 p.Gly64Arg 18596043:181:4
status: NEW183 The G64R, L65R, and M68R mutations preferentially affected P-gp-vinblastine interactions.
X
ABCB1 p.Gly64Arg 18596043:183:4
status: NEW194 TABLE 2 Concentrations of drug substrates required to inhibit cross-linking by 50% Mutant Vinblastine Cyclosporin A Rhodamine B M M M L339C/F728C 0.5 Ϯ 0.2a 0.8 Ϯ 0.3 52 Ϯ 14 G64R/L339C/F728C 53 Ϯ 15b 1.5 Ϯ 0.4 61 Ϯ 10 M68R/L339C/F728C 266 Ϯ 62b 1.3 Ϯ 0.3 57 Ϯ 7 V71R/L339C/F728C 0.6 Ϯ 0.2 0.8 Ϯ 0.2 57 Ϯ 10 a Each value is the mean Ϯ S.D. (n ϭ 3-4 separate cross-linking experiments).
X
ABCB1 p.Gly64Arg 18596043:194:217
status: NEW197 Therefore, we measured drug stimulation of ATPase activity of mutants G64R and M68R using various concentrations of verapamil to test whether the apparent affinity for verapamil of the P-gp mutants was altered.
X
ABCB1 p.Gly64Arg 18596043:197:70
status: NEW200 Accordingly, mutations G64R or M68R were introduced into a wild-type P-gp that contained a histidine tag at the COOH-terminal end.
X
ABCB1 p.Gly64Arg 18596043:200:23
status: NEW201 Histidine-tagged wild-type and mutants G64R and M68R P-gps were expressed in HEK 293 cells, and the proteins were isolated by nickel-chelate chromatography.
X
ABCB1 p.Gly64Arg 18596043:201:39
status: NEW205 Verapamil also stimulated the ATPase activities of mutants G64R and M68R (1.6 and 1.8 mol Pi/min/mg of protein, respectively).
X
ABCB1 p.Gly64Arg 18596043:205:59
status: NEW206 Although both mutants G64R and M68R showed relatively high activation of ATPase activity with verapamil, their apparent affinities for verapamil were reduced by about 19-and 4-fold, respectively.
X
ABCB1 p.Gly64Arg 18596043:206:22
status: NEW207 Half-maximal activation of the ATPase activities of mutants G64R and M68R required 540 m and 120 M verapamil, respectively, compared with 29 m for wild-type P-gp.
X
ABCB1 p.Gly64Arg 18596043:207:60
status: NEW
PMID: 9287132
[PubMed]
Taguchi Y et al: "Amino acid substitutions in the first transmembrane domain (TM1) of P-glycoprotein that alter substrate specificity."
No.
Sentence
Comment
43
Cells transfected with Gly64 -> Arg, or Leu65 -> Arg cDNAs were selected with stepwise increasing concentrations (5, 10, 20 ng/ml) of vinblastine and finally maintained in 20 ng/ ml vinblastine.
X
ABCB1 p.Gly64Arg 9287132:43:23
status: NEW55 From cells transfected with the wild type and He60 -> Arg, His61 -> Arg, Ala63 -> Arg, Gly64 -> Arg, or Leu65 -> Arg mutant cDNA, both Vbl- and Col-resistant colonies were obtained (Fig. 1).
X
ABCB1 p.Gly64Arg 9287132:55:87
status: NEW58 Noticeably, cells transfected with mutant Gly64 -> Arg or Leu65 -> Arg yielded comparable number of Col-resistant colonies, but much less Vbl-resistant colonies, suggesting that the substrate specificities of these two mutants were altered from that of the wild type.
X
ABCB1 p.Gly64Arg 9287132:58:42
status: NEW74 The drug-resistance profiles of the cells expressing He60 -> Arg, His61 -»Arg, Ala63 -»Arg, Gly64 -> Arg, and Leu65 -> Arg mutant P-glycoproteins were investigated by comparing their relative resistance to Vbl, Col, VP16, and Adr (Fig. 3).
X
ABCB1 p.Gly64Arg 9287132:74:102
status: NEW75 The drastic alterations in the drug resistance profile were observed with Gly64 -> Arg or Leu65 -> Arg mutant as well as His61 -»Arg mutant.
X
ABCB1 p.Gly64Arg 9287132:75:74
status: NEW92 The similarity among the substrate specificities of Gly64 -> Arg, Leu65 -> Arg, and His61 -> Arg mutant P-glycoproteins suggest that the amino acid residues at position 64 and 65 are also important in deciding the substrate specificity.
X
ABCB1 p.Gly64Arg 9287132:92:52
status: NEW106 The substrate specificities of the Gly64 -> Arg and Leu65 -> Arg mutants were similar to, but not exactly same with that of the His61 -> Arg mutant.
X
ABCB1 p.Gly64Arg 9287132:106:35
status: NEW107 The cells expressing Gly64 -> Arg or Leu65 -> Arg mutant were more resistant to VP16 than to Vbl, while cells expressing the His61 -* Arg mutant were more resistant to Vbl than to VP16 (Fig. 3).
X
ABCB1 p.Gly64Arg 9287132:107:21
status: NEW
PMID: 26507655
[PubMed]
Loo TW et al: "Mapping the Binding Site of the Inhibitor Tariquidar That Stabilizes the First Transmembrane Domain of P-glycoprotein."
No.
Sentence
Comment
175
In the N-terminal TMD1 domain, the largest number of arginine mutations predicted to line the drug-binding pocket that inhibited tariquidar rescue were located in TM1 (H61R, G64R, L65R, M68R, M69R, and F72R) and TM5 (F303R, I306R, Y307R, S309R, and Y310R) (Fig. 4, A and E).
X
ABCB1 p.Gly64Arg 26507655:175:174
status: NEW193 It was found that 16 of the 28 mutants resembled the G251V/I868R mutant as expression in the presence of 5 òe;M cyclosporine A yielded mature P-gp as the major product in TM1 (H61R, G64R, L65R, M68R, and M69R), TM5 (F303R, I306R, and S309R), TM7 (Q725R and F728R), TM10 (I868R and G872R), TM11 (F942R, T945R, and Q946R), and TM12 (V982R) (Fig. 7).
X
ABCB1 p.Gly64Arg 26507655:193:186
status: NEW283 We identified 13 additional arginine mutations (H61R, G64R, L65R, and M68R in TM1; A129R in TM2; I306R and S309R in TM5; F343R in TM6; F942R, T945R, Q946R, and Y950R in TM11; and L975R in TM12) (Fig. 11A) that were not predicted to lie within 4.5-&#c5; of the predicted site 3 tariquidar-binding site (9).
X
ABCB1 p.Gly64Arg 26507655:283:54
status: NEW313 Therefore, arginines predicted to lie outside of the tariquidar-binding site in TM1 and TM11 in the docking studies (H61R, G64R, L65R, and M68 in TM1; F942R, T945R, Q946R, and Y950R in TM11) might alter interactions between TM1 and TM11.
X
ABCB1 p.Gly64Arg 26507655:313:123
status: NEW