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|Title:||In silico sequence variation analysis of Niemann Pick C1 Like 1 (NPC1L1) gene and its association with cholesterol binding and protein structure stability|
|Authors:||Balgir, Praveen P|
|Keywords:||Alzheimers disease;atherosclerosis;CAD;domains;heterodimeric complex;ICAD;molecular chaperon;multitransmembrane;MuPro;non-synonymous SNPs;NPC1L1;parent-child association;patched family;phylogenetics;sequence similarity;StructureSNP|
|Abstract:||Niemann Pick C1 like 1 (NPC1L1) is a multitransmembrane protein and plays a crucial role in intestinal cholesterol absorption. An in silico approach has been undertaken to decipher its putative functions, other than that in cholesterol absorption, alongwith illustrations on structural domains and other characteristic features. The sequence analysis of the protein states that it belongs to the patched family, sharing a parent-child relationship with it. While phylogenetic analysis provides evidence regarding its early origin in evolution pointing to its participation in more fundamental processes. The effect of non-synonymous (ns) SNPs on the structural stability of the protein as studied by MuPro reveals that substitution of M510I, L1067F, D1071G and E1308K nsSNPs lead to decrease in the stability of the protein. This may potentially affect the structure or function of expressed protein and could, therefore, have an impact on its role in complex diseases conditions like atherosclerosis, Alzheimers disease, etc. The M510I present on the exon 2 of the gene showed 40% sequence similarity with the sequence of CAD (Caspase activated DNase) domain of murine CAD (PDB id IC9F) and its heterodimeric complex ICAD (PDB id 1F2R), as studied by StructureSNP. This points out to the corresponding region acting as a molecular chaperon binding site, playing a potential role in post-translational folding of NPC1L1.|
|ISSN:||0975-0967 (Online); 0972-5849 (Print)|
|Appears in Collections:||IJBT Vol.09(2) [April 2010]|
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