Computational identification of pathogenic associated nsSNPs and its structural impact in UROD gene: a molecular dynamics approach.

Abstract

Uroporphyrinogen decarboxylase is a cytosolic enzyme involved in the biosynthetic pathway of heme production. Decreased activity of this enzyme results in porphyria cutanea tarda and hepato erythropoietic porphyria. Nonsynonymous single nucleotide polymorphisms (nsSNPs) alter protein sequence and can cause disease. Identifying the deleterious nsSNPs that contribute to disease is an important task. We used five different in silico tools namely SIFT, PANTHER, PolyPhen2, SNPs&GO, and I-mutant3 to identify deleterious nsSNPs in UROD gene. Further, we used molecular dynamic (MD) approach to evaluate the impact of deleterious mutations on UROD protein structure. By comparing the results of all the five prediction results, we screened 35 (51.47 %) nsSNPs as highly deleterious. MD analysis results show that all the three L161Q, L282R, and I334T deleterious variants were affecting the UROD protein structural stability and flexibility. Our findings provide strong evidence on the effect of deleterious nsSNPs in UROD gene. A detailed MD study provides a new insight in the conformational changes occurred in the mutant structures of UROD protein.

• Authors: C George Priya Doss, R Magesh
• Journal: Cell biochemistry and biophysics (Cell Biochem Biophys) Vol. 70 Issue 2 Pg. 735-46 (Nov 2014) ISSN: 1559-0283 [Electronic] United States
• PMID: 24777812 (Publication Type: Journal Article)

Chemical References

• Uroporphyrinogen Decarboxylase

Topics

• Disease (genetics)
• Enzyme Stability
• Humans
• Hydrogen Bonding
• Molecular Dynamics Simulation
• Mutation
• Polymorphism, Single Nucleotide
• Protein Structure, Secondary
• Static Electricity
• Uroporphyrinogen Decarboxylase (chemistry, genetics)