ABCMdb

PMID: 21273699

Kumar N, Taneja KK, Kumar A, Nayar D, Taneja B, Aneja S, Behari M, Kalra V, Bansal SK
Novel mutation in ATP-binding domain of ABCD1 gene in adrenoleukodystrophy.
J Genet. 2010 Dec;89(4):473-7., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCD1 p.Arg617Ser The molecular analysis by direct sequencing of the ABCD1 gene showed the presence of a novel missense mutation at c.1849C>A / Arg617Ser in the ATP binding domain in the proband and his mother, further establishing the diagnosis of the disease. Login to comment 24 ABCD1 p.Arg617Ser In this study, we observed a novel point mutation (Arg617Ser) in exon 8 of the ABCD1 gene both in the proband and his mother. Login to comment 40 ABCD1 p.Arg617Ser To explore the role of arginine-617 of ALDP, an Arg617Ser substitution was carried out for the model on a graphics workstation and subjected to the same rounds of minimization. Login to comment 64 ABCD1 p.Arg617Ser The SIFT score of Arg617Ser is 0.00 sorting intolerant from tolerant (SIFT) score 0.05 is predicted to be deleterious). Login to comment 66 ABCD1 p.Arg617Ser These scores suggest that Arg617Ser substitution may affect protein structure which may adversely affect its function. Login to comment 73 ABCD1 p.Arg617Ser In silico analysis was carried out to explore the role of Arg617Ser mutation on binding of ATP. Login to comment 81 ABCD1 p.Arg617Ser Substitution of arginine-617 to serine has an effect on the loop immediately following it includes residues of the Walker B motif and involves in ATP binding (aspartate-629) (figure 2c). Login to comment 86 ABCD1 p.Arg617Ser The proband possessed a novel missense mutation (c.1849C>A/Arg617Ser) in exon 8 of NBD, which is functionally important domain for binding ATP. Login to comment 87 ABCD1 p.Arg617Cys ABCD1 p.Arg617His ABCD1 p.Arg617Leu ABCD1 p.Arg617Gly In this codon, out of six possible different missense mutations, (three each at position first and second of the codon) four viz. c.1849C>T / Arg617Cys, c.1849C>G / Arg617Gly, c.1850G>A / Arg617His and c.1850G>T / Arg617Leu have already been reported by others (Fanen et al. 1994; Krasemann et al. 1996; Coll et al. 2005). Login to comment 93 ABCD1 p.Arg617Ser Superposition of native (black) and Arg617Ser substituted model (gray) of ALDP showed an overall rmsd (root mean square deviation) of 1.4 Å for 100 atoms (residues 605-704). Login to comment 97 ABCD1 p.Arg617Gly fourth case (c.1849C>G/Arg617Gly) the status of formation of ALDP is not reported (Krasemann et al. 1996; Pan et al. 2005). Login to comment 99 ABCD1 p.Arg617Ser ABCD1 p.Arg617Ser This mutation c.1849C>A in exon 8 of ABCD1 gene leads to exchange of amino acid arginine to serine at position 617 in the ALDP (Arg617Ser). Login to comment 106 ABCD1 p.Arg617Ser However, in silico analysis suggests that Arg617Ser mutation located in the Walker B region in the ATP binding domain of ALDP may change pocket size of NBD which may affect ATP binding. Login to comment