ABCMdb

PMID: 25270578

Brewer FK, Follit CA, Vogel PD, Wise JG
In silico screening for inhibitors of p-glycoprotein that target the nucleotide binding domains.
Mol Pharmacol. 2014 Dec;86(6):716-26. doi: 10.1124/mol.114.095414. Epub 2014 Sep 30., [PubMed]

Sentences

No. Mutations Sentence Comment

289 ABCB1 p.Tyr401Leu ABCB1 p.Val801Ser ABCB1 p.Asn428Ala ABCB4 p.Pro1162Thr ABCB1 p.Leu443Val ABCB1 p.Asp521Pro ABCB1 p.Gly430Gln ABCB1 p.Ile160Thr ABCB1 p.Gly525Ser ABCB1 p.Asn1043Glu ABCB1 p.Val1052Ile ABCB1 p.Val524Asn ABCB1 p.His518Tyr ABCB1 p.Tyr1087Pro ABCB1 p.Ser1077Phe ABCB1 p.Gln530Gly ABCB1 p.Tyr444Arg ABCB1 p.Arg905Ala ABCB4 p.Gln1118Asn ABCB1 p.Phe399Leu ABCB1 p.Leu516Asp ABCB4 p.Gly432Leu ABCB1 p.Ser802Thr ABCB1 p.Pro1045His ABCB1 p.Gln1081Leu ABCB1 p.Cys431Val ABCB1 p.Ser429Val ABCB1 p.Phe804Gln ABCB1 p.Gln438Ile ABCB1 p.Leu531Lys ABCB1 p.Ile409Glu ABCB1 p.Lys1164Val ABCB4 p.Gln1280Thr ABCB4 p.Ile585Val ABCB1 p.Arg262Ile ABCB1 p.Asn809Gln ABCB1 p.Thr522Ile ABCB1 p.Phe601Asn ABCB1 p.Tyr1044Ile ABCB1 p.Glu556Thr ABCB1 p.Ile1158Gln ABCB1 p.Pro517Phe ABCB1 p.Thr1078Ile ABCB1 p.Leu1161Gly ABCB1 p.Trp803Thr ABCB1 p.Lys433Asp ABCB1 p.Gln475Ser ABCB1 p.Phe1157Val ABCB1 p.Thr1167Arg ABCB1 p.Ser434Arg ABCB4 p.Asp805Tyr 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