ABCMdb

PMID: 15284228

Kidd JF, Ramjeesingh M, Stratford F, Huan LJ, Bear CE
A heteromeric complex of the two nucleotide binding domains of cystic fibrosis transmembrane conductance regulator (CFTR) mediates ATPase activity.
J Biol Chem. 2004 Oct 1;279(40):41664-9. Epub 2004 Jul 28., 2004-10-01 [PubMed]

Sentences

No. Mutations Sentence Comment

188 ABCC7 p.Lys1250Ala ABCC7 p.Lys464Ala Mutation of the canonical Walker A lysine in either NBD1 (K464A, targeting Site A) or NBD2 (K1250A, targeting Site B) decreased ATPase activity of the whole protein by greater than 50% (39). Login to comment 189 ABCC7 p.Lys1250Ala Interestingly, the most severe effects on ATPase activity and channel gating were observed in the K1250A mutant, wherein ATPase activity was virtually abolished, consistent with this conventional site playing a more important role in generating the overall catalytic function of CFTR. Login to comment 190 ABCC7 p.Asp1370Asn ABCC7 p.Glu1371Ser Unfortunately, there are no ATPase data available for the NBD2 Walker B mutations D1370N and E1371S, which would be expected to severely impair hydrolysis. Login to comment 191 ABCC7 p.Lys1250Ala However, an electrophysiological study found that these mutations caused a marked slowing of channel closing from bursts as did K1250A, which is known to reduce the ATPase activity of CFTR to around 1% of wild type (40). Login to comment 193 ABCC7 p.Lys464Ala Our data suggest that the nonconventional site to which Lys464 contributes (Site A) also participates in the overall activity, since the K464A mutation causes a significant, albeit partial, decrease in function of the full-length protein. Login to comment