ABCMdb

ABCC1 p.Arg593Leu

None has been submitted yet.

Publications

PMID: 15155831 [PubMed] Haimeur A et al: "Mutations of charged amino acids in or near the transmembrane helices of the second membrane spanning domain differentially affect the substrate specificity and transport activity of the multidrug resistance protein MRP1 (ABCC1)."

No. Sentence Comment

51 TTC-3Ј; D430R, 5Ј-C AAC CTC ATG TCT GTG CGC GCT CAG AGG TTC-3Ј; D436K, 5Ј-C GCT CAG AGG TTC ATG AAG TTG GCC ACG TAC-3Ј; D(K)436E, 5Ј-C GCT CAG AGG TTC ATG GAA TTA GCC ACG TAC-3Ј; D572R, 5Ј-C TAC GTG ACC ATT CGC GAG AAC AAC ATC CTG G-3Ј; E573R, 5Ј-C GTG ACC ATT GAC CGG AAC AAC ATC CTG GAT G-3Ј; D578R, 5Ј-G AAC AAC ATC CTG CGG GCC CAG ACA GCC TTC G-3Ј; R593E, 5Ј-G GCC TTG TTC AAC ATC CTC GAG TTT CCC CTG AAC-3Ј; R593L, 5Ј-G GCC TTG TTC AAC ATC CTC CTG TTT CCC CTG AAC-3Ј; R(E)593K, 5Ј-GCC TTG TTC AAC ATC CTT AAG TTT CCC CTG AAC-3Ј. Login to comment
184 In marked contrast, substitutions of TM11 Arg593 with Glu or Leu substantially reduced MRP1 transport activity. Login to comment
185 As shown in Fig. 7, the LTC4 (Fig. 7A), GSH (Fig. 7D), and MTX (Fig. 7E) transport activities of the R593E and the R593L mutants were reduced by 70 to 80% relative to wild-type MRP1. Login to comment
242 Time courses of [3 H]LTC4 uptake (A), [3 H]E217betaG uptake (B), and GSH-stimulated [3 H]E13SO4 uptake (C) by wild-type MRP1 (f), mutants R593E (‚), R593L (ƒ), and R(E)593K (F), and empty pcDNA3.1(-) vector control (E). Login to comment
243 D, apigenin-stimulated [3 H]GSH uptake and [3 H]MTX uptake (E) at 20 min by wild-type (WT) MRP1 (f), mutants R593E, R593L, and R(E)593K (u), and empty pcDNA3.1(-) vector control (Ⅺ). Login to comment
255 Thus, the nonconservatively substituted R593E and R593L mutants displayed a complete loss of E217betaG and E13SO4 transport and a substantial loss of LTC4, GSH, and MTX transport. Login to comment