ABCB1 p.Gly939Cys
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PMID: 10585407
[PubMed]
Loo TW et al: "Identification of residues in the drug-binding domain of human P-glycoprotein. Analysis of transmembrane segment 11 by cysteine-scanning mutagenesis and inhibition by dibromobimane."
No.
Sentence
Comment
117
Mutant G939C had the lowest activity (70% of that of Cys-less P-gp).
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ABCB1 p.Gly939Cys 10585407:117:7
status: NEW120 Fig. 5 shows that the majority of the mutants, except for G939C, F942C, T945C, and Y953C, were not affected by treatment with dBBn.
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ABCB1 p.Gly939Cys 10585407:120:58
status: NEW
PMID: 10681495
[PubMed]
Loo TW et al: "The packing of the transmembrane segments of human multidrug resistance P-glycoprotein is revealed by disulfide cross-linking analysis."
No.
Sentence
Comment
65
Twelve of the 125 P-gp mutants (TM4/TM12 constructs L227C/S993C, V231C/S993C, W232C/S993C, A233C/S993C, I235C/S993C, and L236C/S993C; TM5/TM12 constructs A295C/S993C and I299C/S993C; TM10/TM6 constructs V874C/P350C, E875C/ P350C, and M876C/P350C; and TM11/TM6 construct G939C/ P350C), however, had slower mobilities in SDS-PAGE after treatment with oxidant.
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ABCB1 p.Gly939Cys 10681495:65:270
status: NEW66 A representative result (mutant G939C/P350C) is shown in Fig. 1A.
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ABCB1 p.Gly939Cys 10681495:66:32
status: NEW77 In these cross-linking experiments, the amount of oxidant was lowered by 10-fold (0.2 mM), and the minimum temperature required to induce cross-TABLE I Cross-linking analysis of P-gp Cross-linking of S993C (TM12) with residues in the following TM: TM1 TM2 TM3 TM4 TM5 M51C -a Y130C - G185C - G226C - I293C - V52C - I131C - I186C - L227C ϩb T294C - V53C - Q132C - G187C - S228C - A295C ϩ G54C - V133C - D188C - A229C - N296C - T55C - S134C - K189C - A230C - I297C - L56C - F135C - I190C - V231C ϩ S298C - A57C - W136C - G191C - W232C ϩ I299C ϩ A58C - C137C - M192C - A233C ϩ G300C - I59C - L138C - F193C - K234C - A301C - I60C - A139C - F194C - I235C ϩ A302C - H61C - A140C - Q195C - L236C ϩ F303C - G141C - S196C - S237C - L304C - Cross-linking of P350C (TM6) with residues in the following TM: TM7 TM8 TM9 TM10 TM11 F711C - F770C - A828C - I867C - A935C - V712C - F771C - I829C - I868C - H936C - V713C - L772C - G830C - A869C - I937C - G714C - Q773C - S831C - I870C - F938C - V715C - G774C - R832C - A871C - G939C ϩ F716C - F775C - L833C - G872C - I940C - C717C - T776C - A834C - V873C - T941C - A718C - F777C - V835C - V874C ϩ F942C - I719C - G778C - I836C - E875C ϩ S943C - I720C - K779C - T837C - M876C ϩ F944C - N721C - A780C - Q838C - K877C - T945C - G722C - G781C - N839C - M878C - Q946C - G723C - E782C - I840C - L879C - A947C - I783C - a -, no cross-linked product detected in SDS-PAGE. b ϩ, cross-linked product detected in SDS-PAGE.
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ABCB1 p.Gly939Cys 10681495:77:1057
status: NEW79 A representative result (mutant G939C/P350C) is shown in Fig. 1C.
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ABCB1 p.Gly939Cys 10681495:79:32
status: NEW99 Mutants L227C/S993C, V231C/ S993C, W232C/S993C, A233C/S993C, I235C/S993C, L236C/ S993C, A295C/S993C, I299C/S993C, V874C/P350C, E875C/ P350C, M876C/P350C, and G939C/P350C were inhibited by 81, 88, 90, 89, 93, 81, 78, 87, 87, 77, 70, and 78%, respectively.
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ABCB1 p.Gly939Cys 10681495:99:158
status: NEW110 Oxidative cross-linking of P-gp mutant G939C/P350C.
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ABCB1 p.Gly939Cys 10681495:110:39
status: NEW111 A, membranes from HEK 293 cells transfected with vector alone (Control), mutant G939C/P350C, or Cys-less (C-less) P-gp cDNA were treated for 10 min at 37 °C in the presence (ϩ) or absence (-) of 2 mM Cu2ϩ (phenanthroline)3.
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ABCB1 p.Gly939Cys 10681495:111:80
status: NEW115 C, membranes from HEK 293 cells expressing mutant G939C/P350C were treated with 0.2 mM Cu2ϩ (phenanthroline)3 in the presence of no drug (None), 1 mM colchicine (Colch), 0.15 mM verapamil (Ver), 10 M cyclosporin A (Cyclo) or 35 M vinblastine (Vin) or in the presence of no addition (None), 5 mM ATP (ATP), 5 mM ATP and 0.1 mM vanadate (ATP/VO4) or 0.1 mM vanadate (VO4).
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ABCB1 p.Gly939Cys 10681495:115:50
status: NEW118 TABLE II Minimum temperature required for cross-linking Residues TM segments 4 °C 21 °C 37 °C L227C/S993C 4/12 -a - ϩ V231C/S993C 4/12 - ϩ ϩ W232C/S993C 4/12 - ϩ ϩ A233C/S993C 4/12 ϩb ϩ ϩ I235C/S993C 4/12 ϩ ϩ ϩ L236C/S993C 4/12 ϩ ϩ ϩ A295C/S993C 5/12 - ϩ ϩ I299C/S993C 5/12 ϩ ϩ ϩ V874C/P350C 10/6 - ϩ ϩ E875C/P350C 10/6 - - ϩ M876C/P350C 10/6 - ϩ ϩ G939C/P350C 11/6 - ϩ ϩ a -, no cross-linked product detected in SDS-PAGE. b ϩ, cross-linked product detected in SDS-PAGE.
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ABCB1 p.Gly939Cys 10681495:118:508
status: NEW
PMID: 12609990
[PubMed]
Loo TW et al: "Substrate-induced conformational changes in the transmembrane segments of human P-glycoprotein. Direct evidence for the substrate-induced fit mechanism for drug binding."
No.
Sentence
Comment
91
In mutant P350C(TM6)/G939C- (TM11), progesterone was more efficient in promoting cross-linking than cyclosporin A.
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ABCB1 p.Gly939Cys 12609990:91:21
status: NEW124 In the presence of drug substrate (progesterone), TM segments 11 and 12 undergo rotational and/or lateral movements so that cross-linking can occur between P350C and V991C (black ball) in TM12 and with A935C (red ball) and G939C (turquoise ball) in TM11.
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ABCB1 p.Gly939Cys 12609990:124:223
status: NEW135 The presence of progesterone, however, promoted cross-linking of residue P350C(TM6) with two residues in TM 11 (A935C and G939C) and to residue V991C in TM12.
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ABCB1 p.Gly939Cys 12609990:135:122
status: NEW142 When the residues in TM11 are modeled as an ␣-helical wheel, residues A935 and G939C are found on the same face of the TM segment (Fig. 5B).
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ABCB1 p.Gly939Cys 12609990:142:86
status: NEW144 Cyclosporin A also promoted cross-linking between TM6 and TM11, but only between P350C and G939C.
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ABCB1 p.Gly939Cys 12609990:144:91
status: NEW
PMID: 14749322
[PubMed]
Loo TW et al: "Val133 and Cys137 in transmembrane segment 2 are close to Arg935 and Gly939 in transmembrane segment 11 of human P-glycoprotein."
No.
Sentence
Comment
115
Disulfide cross-linking of P-gp mutants. Membranes were prepared from HEK 293 cells expressing P-gp mutant V133C(TM2), G939C(TM11), C137C(TM2), A935C(TM11), V133C(TM2)/G939C (TM11), or C137C(TM2)/A935C(TM11).
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ABCB1 p.Gly939Cys 14749322:115:168
status: NEW124 TABLE I Cross-linking between residues in TM2 and TM11 -, no cross-linked product detected on SDS-polyacrylamide gels at 37 °C; ϩ, relatively weak cross-linking (Ͻ50% of P-gp cross-linked) at 37 °C; ϩϩ, relatively strong cross-linking (Ͼ50% of P-gp cross-linked) at 37 °C; *, cross-linked product also detected at 22 °C; **, cross-linked product also detected at 22 and 4 °C. TM2 TM11 A935C H936C I937C F938C G939C I940C T941C F942C S943C F944C A128C - - - - - - - - - - A129C - - - - - - - - - - Y130C - - - - ϩ ϩ - ϩ ϩ - I131C - - - - - - - - - - Q132C - - - - - - - - - - V133C - - - ϩ ϩϩ, ** - - ϩ ϩ - S134C ϩ ϩ - - ϩ ϩ - - - - F135C - - - - - - - - - - W136C - - - - - - - - - - C137C ϩϩ, ** - - - ϩ - - - - - L138C ϩϩ, * - - - - - - - - - TM11 are close to each other at their cytoplasmic ends.
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ABCB1 p.Gly939Cys 14749322:124:464
status: NEW