Significance of Knotted Structures for Function of Proteins and Nucleic Acids - September 17-21, 2014

Significance of Knotted Structures for Function of Proteins and Nucleic Acids

Poster Session II

37 – POS Board 9 Comparison of Orthologous Proteins: Knotted and Unknotted Agata P. Perlińska 1 , Joanna I. Sulkowska 1,2 1 Centre of New Technology, University of Warsaw, Poland. 2 Faculty of Chemistry, University of Warsaw, Poland Knots are complex structures which exist both in macro and microscopic world. Since first knots in proteins were noticed 20 years ago many more proteins with even more complex knots have been discovered. To this day their origin is unknown but their presence in all three domains of life suggests that, since they weren’t eliminated by natural selection, they must serve an important role in a cell. Knots appear to have more stable topology than other protein folds and it can be established by comparing orthologous proteins, knotted and unknotted. Using molecular dynamics on analogous pairs of proteins from methyltransferases we identified, that there is a difference in stability between knot fold and Rossmann fold, Rossmann fold is less stable. Additional difference is observed in dynamics between simulations with and without ligands. Also examined were the conformations of a ligand in the active site of those analogous proteins and it revealed clear trend where ligand prefers to take L-shaped conformations in knotted proteins and I-shaped in unknotted. This subject is worth investigating further because many of those methyltransferases are important enzymes and thanks to the different ligand conformations forced by the different folds it could be possible to create specific inhibitors for the knotted proteins.

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