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Influence of the SNPs on the structural stability of CBS protein: Insight from molecular dynamics simulations
, Rajith B, , Ashish Kumar A.
Published in Springer Science and Business Media LLC
Volume: 9
Issue: 6
Pages: 504 - 518
Cystathionine β-synthase is an essential enzyme of the trans-sulfuration pathway that condenses serine with homocysteine to form cystathionine. Missense mutations in CBS are the major cause of inherited homocystinuria, and the detailed effect of disease associated amino acid substitutions on the structure and stability of human CBS is yet unknown. Here, we apply a unique approach in combining in silico tools and molecular dynamics simulation to provide structural and functional insight into the effect of SNP on the stability and activity of mutant CBS. In addition, principal component analysis and free energy landscape were used to predict the collective motions, thermodynamic stabilities and essential subspace relevant to CBS function. The obtained results indicate that C109R, E176K and D376N mutations have the diverse effect on dynamic behavior of CBS protein. We found that highly conserved D376N mutation, which is present in the active pocket, affects the protein folding mechanism. Our strategy may provide a way in near future to understand and study effects of functional nsSNPs and their role in causing homocystinuria. © 2014, Higher Education Press and Springer-Verlag Berlin Heidelberg.
About the journal
JournalData powered by TypesetFrontiers in Biology
PublisherData powered by TypesetSpringer Science and Business Media LLC
Open AccessNo