ABCMdb

ABCB1 p.Val53Cys

None has been submitted yet.

Publications

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

77 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. Login to comment

PMID: 15709779 [PubMed] Kaur P et al: "Biochemical characterization of domains in the membrane subunit DrrB that interact with the ABC subunit DrrA: identification of a conserved motif."

No. Sentence Comment

77 The mutants were named S4C, S15C, S23C, S35C, A44C, C260S up: 5'-GGCCTGGTCCTGTCCGTGTCGGCAGGG-3' C260S dn: 5'-CCCTGCCGACACGGACAGGACCAGGCC-3' S23C up: 5'- CGGACGGTGCTGTGCGCGGGTGAACGG-3' S23C dn: 5'- CCGTTCACCCGCGCACAGCACCGTCCG-3' V53C, T70C, S80C, V92C, S107C, V116C, A129C, T149C, A160C, V173C, S213C, S236C, T249C, A270C, and A282C, respectively. Login to comment
168 substitutions, including V53C, T70C, V92C, A129C, S236C, and S249C, showed a decrease in resistance to doxorubicin (Table 1). Login to comment
187 (B) A44C, V53C, T70C, V92C, S107C, and V116C. Login to comment
196 Table 1: Doxorubicin Resistance of E. coli N43 Cells Expressing Wild Type DrrA with DrrB Containing Different Cysteine Substitutionsa amt of dox, µg/mLdomain of DrrB location of cysteine 0 4 6 8 (wild type) C260 +++ +++ +++ ++ N-terminus S15C +++ +++ +++ ++ N-terminus S23C +++ +++ +++ ++ N-terminus S35C +++ +++ ++ ++ N-terminus A44C +++ +++ ++ + TM 1 V53C +++ ++ ++ - TM 1 T70C +++ + + + P 1 S80C +++ ++ + - TM 2 V92C +++ ( - - TM 2 S107C +++ +++ ++ ++ C 1 V116C +++ +++ +++ ++ TM 3 A129C +++ ++ + - TM 4 T149C +++ ++ ++ + C 2 A160C +++ +++ ++ + TM 5 V173C +++ +++ ++ + TM 6 S213C +++ +++ ++ + C 3 S236C +++ ++ + - TM 7 S249C +++ + + - TM 8 A270C +++ +++ ++ ++ C-terminus A282C +++ +++ ++ ++ cysteine-less DrrB C260S +++ +++ +++ +++ vector only pSU2718 ++++ ( - - a Legend: +++, very good growth; ++, good growth; +, some growth; -, no growth. Login to comment
214 Analysis of the mutants in TM1 (V53C and T70C) and TM2 (V92C and S107C) also showed the 60 kDa cross-linked species containing DrrA and DrrB (Figure 4B). Login to comment
278 Six (V53C, T70C, V92C, A129C, S236C, S249C) out of 20 substitutions created in this study, however, showed varying levels of doxorubicin-sensitive phenotype (Table 1). Login to comment
281 Secondary structure analysis by the Chou-Fasman method showed that five (V53C, T70C, V92C, A129C, S249C) of these six mutants, which resulted in doxorubicin sensitivity, showed no change at all in their predicted secondary structure, the exception being S236C, which showed a split in the helical stretch predicted between residues 226 and 248 in the C terminus of DrrB. Login to comment

PMID: 16492138 [PubMed] Loo TW et al: "Transmembrane segment 1 of human P-glycoprotein contributes to the drug-binding pocket."

No. Sentence Comment

98 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. Login to comment