ABCMdb

ABCB1 p.Tyr401Leu

None has been submitted yet.

Publications

PMID: 16768456 [PubMed] Kim IW et al: "The conserved tyrosine residues 401 and 1044 in ATP sites of human P-glycoprotein are critical for ATP binding and hydrolysis: evidence for a conserved subdomain, the A-loop in the ATP-binding cassette."

No. Sentence Comment

86 HighFive insect cells (Invitrogen) were infected with the recombinant baculovirus carrying the wild type and Y401A, Y1044A, Y401A/Y1044A, Y401C, Y401L, and Y401W mutant human MDR1 cDNAs with a His6 tag at the C-terminal end [BV-MDR1(His6)] as described previously (37). Login to comment
100 The Pgp‚Mg-8-azido[R-32 P]ADP‚ BeFx or Pgp‚Mg-8-azido[R-32 P]ADP‚Vi preor posthydrolysis transition state conformation was generated as described Table 1: Effect of Substitution of the Conserved Y401 and Y1044 Residues in ATP Sites on Pgp Cell Surface Expression, Transport Function, ATP Binding, Nucleotide Trapping, and Hydrolysisa construct cell surface expressionb (%) transport functionc (%) ATP bindingd (%) ADP-Vi trappinge (%) ATP hydrolysisf (%) wild-type MDR1 100 100 100 100 100 Y401W 100 100 90-95 90-95 85-90 Y401F 95-100 90-100 NTg NTg NTg Y401C 90-95 45-55 50 <20 NTg Y401L 95-100 25-30 30-35 20-25 NTg Y401A 100-110 <2 <15 <2 <2 Y1044W 100 100 NTg NTg NTg Y1044F 95-100 90-100 NTg NTg NTg Y1044C 90-95 <2 NTg NTg NTg Y1044A 100 <2 <5 <2 <2 Y401W/Y1044W 90-95 <2 NTg NTg NTg Y401F/Y1044F 90-95 95-100 NTg NTg NTg Y401C/Y1044C 100 <2 NTg NTg NTg Y401A/Y1044A 90-95 <2 <2 <2 <2 Y401F/Y1044W 100 100 NTg NTg NTg Y401C/Y1044W 100 <2 NTg NTg NTg Y401A/Y1044W 100-110 <2 NTg NTg NTg Y401W/Y1044F 100 100 NTg NTg NTg a The levels of cell surface expression, transport activity, ATP binding, nucleotide trapping, and ATP hydrolysis by the wild-type protein were taken to be 100%, and these activities in mutant Pgps were expressed relative to wild-type levels. Login to comment
144 We generated the single mutants Y401A, Y1044A, Y401C, Y1044C, Y401F, Y1044F, Y401W, Y1044W, and Y401L. Login to comment
153 Figure 2 illustrates that in a flow cytometry assay HeLa cells expressing wild-type Pgp show a reduced level of accumulation of fluorescent calcein, whereas cells expressing equivalent amounts of Y401L and Y401C mutant Pgps show partial (30-50%) transport function (Table 1). Login to comment
169 Binding of 8-Azido[R-32 P]ATP to Wild-Type, Y401A, Y1044A, Y401A/Y1044A, Y401W, Y401C, and Y401L Mutant Pgps. Login to comment
175 In Y401L and Y401C mutants, 30-50% of the azidonucleotide was incorporated. Login to comment
200 cross-linking with 8-azidoATP at 4 °C, both Y401L and Y401C trap ~20% nucleotide in the presence of vanadate (Table 1). Login to comment
264 Similar results were also obtained with Y401L and Y401C mutants (see Table 1). Login to comment
297 Consistent with this view is the fact that while mutants Y401L and Y401C are partially (30-50%) functional, mutants Y1044C and Y401C/Y1044C are completely nonfunctional (Table 1). Login to comment

PMID: 18058211 [PubMed] Sauna ZE et al: "Genomics and the mechanism of P-glycoprotein (ABCB1)."

No. Sentence Comment

78 Y401C and Y401L mutant P-gps showed partial (30-50%) transport function. Login to comment

PMID: 25270578 [PubMed] Brewer FK et al: "In silico screening for inhibitors of p-glycoprotein that target the nucleotide binding domains."

No. Sentence Comment

289 TABLE 2 Identification of protein residues in P-gp that were within 5.0 &#c5; of docked inhibitors Compound Compound 19 (ATP-binding site) Compound 29 (Allosteric binding site) Compound 34 (ADP-binding site) Compound 45 (ATP-binding site) Residues within 5.0 &#c5; of docked inhibitors ILE 160 THR 422 ARG 262 ILE 160 GLY 161 VAL 423 THR 483 GLY 161 ASP 164 ALA 424 LEU 516 ASP 164 PHE 399 LEU 552 PRO 517 PHE 399 TYR 401 LEU 554 HIS 518 TYR 401 PRO 402 THR 563 ASP 521 PRO 402 ILE 409 GLU 566 THR 522 ILE 409 ASN 428 ALA 567 LEU 523 LEU 410 SER 429 VAL 569 VAL 524 ASN 428 GLY 430 GLN 570 GLY 525 SER 429 CYS 431 VAL 571 GLU 526 GLY 430 GLY 432 LEU 573 ALA 529 CYS 431 LYS 433 ASP 574 GLN 530 GLY 432 SER 434 ARG 577 LEU 531 LYS 433 THR 435 THR 582 VAL 801 SER 434 GLN 438 ILE 583 SER 802 THR 435 LEU 443 VAL 584 TRP 803 THR 436 TYR 444 ARG 588 PHE 804 GLN 438 GLN 475 SER 590 ASP 805 TYR 444 GLU 556 THR 591 ASN 809 GLN 475 ILE 585 VAL 592 ASN 1043 GLU 556 HIS 587 ARG 593 TYR 1044 ILE 585 PHE 601 ASN 594 PRO 1045 HIS 587 ARG 905 ALA 595 ARG 1047 ARG 905 ILE 1127 ASP 596 VAL 1052 ILE 1127 PHE 1157 VAL 1273 SER 1077 PHE 1157 ILE 1158 GLN 1274 THR 1078 ILE 1158 LEU 1161 GLY 1276 GLN 1081 LEU 1161 PRO 1162 THR 1277 TYR 1087 PRO 1162 ASN 1163 LYS 1278 GLN 1118 ASN 1163 THR 1167 ARG 1279 LYS 1164 VAL 1169 GLN 1280 THR 1167 THR 1174 THR 1174 GLN 1175 GLN 1175 LEU 1176 LEU 1176 SER 1177 SER 1177 GLY 1178 GLY 1178 GLY 1179 GLY 1179 GLN 1180 GLN 1180 Other groups have shown that flavonoids are strong modulators of P-gp activity and that they interact with the NBDs of the enzyme (Di Pietro et al., 2002). Login to comment