ABCMdb

PMID: 16554808

Gadsby DC, Vergani P, Csanady L
The ABC protein turned chloride channel whose failure causes cystic fibrosis.
Nature. 2006 Mar 23;440(7083):477-83., 2006-03-23 [PubMed]

Sentences

No. Mutations Sentence Comment

139 ABCC7 p.Lys1250Ala ABCC7 p.Lys1250Ala ABCC7 p.Lys464Ala ABCC7 p.Lys464Ala But they are 11 22 11 2 a b ATP ATP ATP ATP C2 Open Concentration of MgATP in µM Relativeopeningrate K1250A K464A C1C0 101 1.0 WT K464A K1250A 0.5 0 102 103 104 Figure 3 | The conserved Walker A lysine is critical for ATP binding in each NBD. Login to comment 144 ABCC7 p.Lys1250Ala ABCC7 p.Lys464Ala ATP first binds to the non-mutant site, that is to the NBD2 site (blue) in K464A channels (upper row), but to the NDB1 site (green) in K1250A channels (lower row). Login to comment 147 ABCC7 p.Glu1371Gln Comparison of speed of closing of wild-type CFTR (a) and of mutant CFTR bearing the single mutation E1371Q (b), of the conserved Walker B glutamate. Login to comment 149 ABCC7 p.Glu1371Gln The greatly delayed closing of all four E1371Q channels (b), compared with the four WT CFTR channels (a), after removal of ATP supports the conclusion that ATP hydrolysis at the NBD2 composite catalytic site controls normal channel closing63-66,72-77,80 , and that the channel open-burst state corresponds to NBD dimerization22,29,69,70,80 . Login to comment 150 ABCC7 p.Glu1371Gln E1371Q ATPATP WT 0.5 pA 60 s a b opened only inefficiently by millimolar concentrations of poorly hydrolysable analogues such as AMP-PNP, AMP-PCP or ATP-γS53,62-64 , and not at all by ADP62 . Login to comment 174 ABCC7 p.Glu1371Gln ABCC7 p.Glu1371Gln One clue that the CFTR-channel open state corresponds to the heterodimerized NBD1-NBD2 conformation comes from the ~1,000-fold stabilization of the open state (Fig. 4b) caused by the mutation E1371Q of the Walker B Glu (the possible catalytic base29,81 ). Login to comment