ABCB1 p.His61Cys
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PMID: 16492138
[PubMed]
Loo TW et al: "Transmembrane segment 1 of human P-glycoprotein contributes to the drug-binding pocket."
No.
Sentence
Comment
97
Table 1 shows that all mutants, except for mutants H61C and G64C, showed characteristics similar to that Table 1 Drug-stimulated ATPase activity of TM1 cysteine mutants ND, not determined because of very low expression.
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ABCB1 p.His61Cys 16492138:97:51
status: NEW98 Verapamil Colchicine Vinblastine Mutant Vmax (%)* S50 (µM)† Vmax (%) S50 (µM) Vmax (%) S50 (µM) M51C 101 11.0 + - 0.6 96 391 + - 36 94 2.4 + - 0.2 V52C ND ND ND ND ND ND V53C 104 12.0 + - 0.2 101 389 + - 30 102 2.2 + - 0.1 G54C ND ND ND ND ND ND T55C 114 10.3 + - 1.1 95 418 + - 22 91 2.2 + - 0.1 L56C 103 12.2 + - 0.3 87 440 + - 41 95 2.5 + - 0.2 A57C 108 11.3 + - 0.3 98 377 + - 34 92 2.4 + - 0.2 A58C 90 12.5 + - 0.2 94 434 + - 20 95 2.6 + - 0.3 I59C 115 11.2 + - 0.8 95 380 + - 33 114 2.5 + - 0.2 I60C 102 11.1 + - 0.7 91 408 + - 18 110 2.5 + - 0.2 H61C 97 54.0 + - 5.0 61 912 + - 86 105 5.4 + - 0.4 G62C ND ND ND ND ND ND A63C 114 10.5 + - 1.2 99 362 + - 42 105 2.0 + - 0.3 G64C 106 45.0 + - 6.0 88 613 + - 55 60 2.4 + - 0.1 L65C 72 9.3 + - 1.1 112 368 + - 32 78 2.0 + - 0.2 P66C 95 13.0 + - 0.5 86 480 + - 39 97 2.8 + - 0.4 L67C 101 12.3 + - 0.3 106 423 + - 21 100 2.3 + - 0.1 M68C 119 9.7 + - 1.1 105 365 + - 32 92 2.3 + - 0.2 M69C 107 11.8 + - 0.6 110 431 + - 25 108 2.2 + - 0.1 L70C 94 11.4 + - 0.7 90 413 + - 18 98 2.3 + - 0.1 V71C 106 11.9 + - 0.3 90 370 + - 27 102 2.5 + - 0.5 Cys-less 100 12.0 + - 1.0 100 412 + - 48 100 2.2 + - 0.3 * Maximum activity relative to that of Cys-less P-gp.
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ABCB1 p.His61Cys 16492138:98:575
status: NEW101 Mutants H61C and G64C showed approx.
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ABCB1 p.His61Cys 16492138:101:8
status: NEW103 Mutant H61C also exhibited a reduction in the apparent affinity for vinblastine.
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ABCB1 p.His61Cys 16492138:103:7
status: NEW199 We also found that mutation of either His61 or Gly64 to cysteine altered the apparent affinity of P-gp for verapamil, colchicine or vinblastine (Table 1).
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ABCB1 p.His61Cys 16492138:199:38
status: NEW200 Arrangement of the residues in TM1 in a cylindrical helix (Figure 8A) shows that residues that react with MTS-verapamil (L65C; the present study) show alterations in substrate specificity when mutated (H61C, G644C and L65C; [44,45]) or show ATP-dependent cross-linking (M68 and M69; [30]) and occupy one face of the helix.
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ABCB1 p.His61Cys 16492138:200:202
status: NEW215 Residues that show alterations in substrate specificity when mutated (H61C, G644C and L65C, circled) or show ATP-dependent cross-linking (Met68 and Met69 , boxed) with residues in TM11 are shown as occupying one face of the helix.
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ABCB1 p.His61Cys 16492138:215:70
status: NEW