Mg2+ vs Ca2+ bound active site of group II intron– A MD study

Publication date: Available online 23 January 2020Source: Journal of Molecular Graphics and ModellingAuthor(s): Abhishek Kumar, Priyadarshi SatpatiAbstractGroup II introns are enzymes which undergo self-splicing and remove itself from pre-messenger RNA. X-ray structures of group II intron of Oceanobacillus iheyensis at various stages of the self-splicing pathway (pre-hydrolytic, post-hydrolytic, and ligand-free state) revealed intricate atomic interaction network in the active site of the intron. It has been confirmed that a heteronuclear metal ion cluster consisting of four metal ions (K1, K2 sites with K+ and M1, M2 sites with Mg2+) are crucial for function. Substitution of Mg2+ by Ca2+ results in loss of enzymatic activity. The X-ray structures not only opens up the possibility of modelling Mg2+ and Ca2+ bound active site of group II intron and quantitatively estimate the energetics of Mg2+ vs Ca2+ preference but also explore the relative structural and dynamical differences in response to divalent metal ion substitution. Thus, using X-ray structures as a template we performed molecular dynamics simulations to compare structural and dynamical differences between Mg2+ and Ca2+ bound active site of group II intron at various stages of the splicing pathway (i.e, pre-hydrolytic, post-hydrolytic, and ligand-free state). Quantitative estimation of Mg2+ vs Ca2+ selectivity at the M1, M2 sites confirmed Mg2+ preference at intron active sites relative to Ca2+. Ca2+ is relatively mo...
Source: Journal of Molecular Graphics and Modelling - Category: Molecular Biology Source Type: research