Document Type: Original Article

Authors

1 MD, PhD, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

2 MD, PhD, legal medicine research center, legal medicine organization, Tehran , iran

3 MD, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

4 PhD, Department of Biotechnology, Institute of Science and High Technology and Environmental Science, Graduate University of Advanced Technology, Kerman, Iran

5 MD, Genetic Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Cholestatic disorders are divided in the extra and intra-hepatic that created due to the severe liver diseases. ABCB11 encodes the bile salt export pump and this gene is mutated in several forms of intrahepatic cholestasis. So far, some molecular features of this gene was studies.
Objective: Using a developed web server, we identified high number of rare codons in this gene, and four cases were related to BSEP-deficient patients which can be used for drug design.
Material and Methods: By in-silico modelling of ABCB11, some of rare codons in different locations of ATP8b1 gene were identified and evaluated. Using several web servers a number of mutations that converted non-rare codons to rare codon in these patients were identified.
Results: Some of these rare Codons were located at special positions by mutation of which, the new side chains do not seem suitable for protein structure and function. Furthermore, this mutation changed the protein folding rate that may have a critical role in proper folding. Thus, primary change of these codons contributes to BSEP deficiency.
Conclusion: This work is a comprehensive analysis of rare codons of ABCB11 and assessment of a number of these rare codon in protein levels. Rare codons evaluation can enhance our understanding of ABCB11 structural protein of ABCB11, and help us to develop mutation-specific therapies in design of new drugs.

Keywords

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