ABCMdb

PMID: 24483936

Lentini L, Melfi R, Di Leonardo A, Spinello A, Barone G, Pace A, Palumbo Piccionello A, Pibiri I
Toward a rationale for the PTC124 (Ataluren) promoted readthrough of premature stop codons: a computational approach and GFP-reporter cell-based assay.
Mol Pharm. 2014 Mar 3;11(3):653-64. doi: 10.1021/mp400230s. Epub 2014 Feb 7., [PubMed]

Sentences

No. Mutations Sentence Comment

12 ABCC7 p.Gly542* The most commonly observed mutations include deletion of a codon at position 508 (delta-F508), a missense mutation at position 551, and a nonsense mutation at position 542 (G542X).34 Cystic fibrosis patients with nonsense-mutation essentially produce no CFTR protein, thus suffering a more severe form of the disease. Login to comment 16 ABCC7 p.Gly542* Therefore, we performed the first computational study to investigate putative codon-specific supramolecular interactions between the PTC124 and an 11 codon long sequence corresponding to the CFTR fragment coding mRNA bearing a G542X nonsense mutation (i.e., UGA at position 542). Login to comment 158 ABCC7 p.Gly542* Five MD simulations of 100 ns were conducted on the complex between the 1,2,4-oxadiazole ligand (PTC124), and four models of mRNA constituted by a sequence of 33 ribonucleotides of the CFTR gene, that differ in the identity of the central codon normally expressing aminoacid 542: (i) GGA, as found in the wild type mRNA; (ii) UGA, mimicking the G542X nonsense mutation; (iii) UAG, and (iv) UAA, representing the other two types of premature stop codons. Login to comment