ABCB3 p.Val656Leu
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PMID: 25886173
[PubMed]
Golin J et al: "The multidrug transporter Pdr5 on the 25th anniversary of its discovery: an important model for the study of asymmetric ABC transporters."
No.
Sentence
Comment
160
Perhaps the most important mutant in the collection was a V656L substitution that lies in cis orientation in ICL2 with respect to the Q-loop [19,20].
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ABCB3 p.Val656Leu 25886173:160:58
status: NEW165 Further evidence for the cis interface came from our observation that V656L was also a strong suppressor of the cis Q-loop drug-hypersensitive mutation E244G.
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ABCB3 p.Val656Leu 25886173:165:70
status: NEW200 Therefore these mutants altered the stimulation signal, much like S558Y, V656L and V656A altered the trans-inhibition of Pdr5 ATPase by clotrimazole [18-20].
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ABCB3 p.Val656Leu 25886173:200:73
status: NEW208 Three, V656L, P596L and A670S, were in regions making up the predicted Pdr5 signal interface (V656L and P596L were also represented in our suppressor mutant hunt).
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ABCB3 p.Val656Leu 25886173:208:7
status: NEWX
ABCB3 p.Val656Leu 25886173:208:94
status: NEW209 Clues about how these alleles might manipulate the interface to create greater drug resistance came from our in-depth study of V656L [20].
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ABCB3 p.Val656Leu 25886173:209:127
status: NEW213 Furthermore, whereas the V656L suppression of E244G restored drug-resistance to WT levels, the reduced level of ATPase activity seen in the E244G mutant remained.
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ABCB3 p.Val656Leu 25886173:213:25
status: NEW214 Taken together, the behaviour of V656L and the E244G/V656L double mutant suggested that the V656L substitution increased resistance in one of two ways. It is plausible that the V656L mutant increases the efficiency with which the energy from ATP binding and/or hydrolysis is used for transport.
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ABCB3 p.Val656Leu 25886173:214:33
status: NEWX
ABCB3 p.Val656Leu 25886173:214:53
status: NEWX
ABCB3 p.Val656Leu 25886173:214:92
status: NEWX
ABCB3 p.Val656Leu 25886173:214:177
status: NEW