ABCMdb

PMID: 22752155

Galfre E, Galeno L, Moran O
A potentiator induces conformational changes on the recombinant CFTR nucleotide binding domains in solution.
Cell Mol Life Sci. 2012 Nov;69(21):3701-13. doi: 10.1007/s00018-012-1049-7. Epub 2012 Jul 3., [PubMed]

Sentences

No. Mutations Sentence Comment

14 ABCC7 p.Gly551Asp Other mutations, such as the relatively frequent mutation G551D, severely impair CFTR gating (class III), reducing the ion transport. Login to comment 36 ABCC7 p.Gly551Asp ABCC7 p.Gly1349Asp This hypothesis is supported by the observation that mutations in conserved residues of the NBDs, such as G551D and G1349D, exhibit a shift in the affinity for potentiators [14, 23-25]. Login to comment 38 ABCC7 p.Gly551Asp ABCC7 p.Gly1349Asp With the aim of identifying the activating binding site of potentiators, we modelled the NBD dimer [25], and compared the theoretical binding-free energy of several compounds docked on the model, with the experimental binding-free energy obtained from dissociation constants from wild-type, G551D, and G1349D proteins. Login to comment 190 ABCC7 p.Gly551Asp This has recently been demonstrated after the completion of the third phase of the clinical trial for the CFTR potentiator, VX-770 (Ivacaftor, Kalydeco), that it can ameliorate most clinical parameters of CF patients carrying mutation G551D, the third most abundant in the world [42-46]. Login to comment 191 ABCC7 p.Gly551Asp This has recently been demonstrated after the completion of the third phase of the clinical trial for the CFTR potentiator, VX-770 (Ivacaftor, Kalydeco), that it can ameliorate most clinical parameters of CF patients carrying mutation G551D, the third most abundant in the world [42-46]. Login to comment