Analysis of Binding Specificity of Rossmann Fold Methyltransferases
||Analysis of Binding Specificity of Rossmann Fold Methyltransferases|
||SNIC Small Compute|
||Jasmine Gardner <firstname.lastname@example.org>|
||2020-09-25 – 2021-10-01|
The Rossmann Fold class of proteins is a diverse set of enzymes with a conserved beta-alpha-beta fold which acts in binding nucleotide cofactors, including nicotinamide adenine dinucleotide (NAD), flavin adenine dinucleotide (FAD), and S-adenosylmethionine (SAM). Despite being highly-conserved structurally, Rossmann Fold proteins exhibit varied sequences and binding interactions. Previous studies based on NAD and NADP+ binding uncovered that Rossmann Fold proteins can be nucleotide specific with small changes in sequence. This study further showed the ability to directly engineer Rossmann Fold proteins to favor the unnatural cofactor. SAM-binding Rossmann Fold Methyltransferases (MTases) are an important class within the Rossmann Fold class which catalyze the transfer of a methyl group to DNA, RNA, lipids, or other substrates. Despite important biological function, the binding motifs associated with cofactor specificity have not been identified. Recently, our experimental collaborators have discovered a conserved motif which aids in specifically binding the adenine moiety of SAM. Further collaborative work identified additional conserved residues which are spatially consistent. The relationship between these conserved binding residues and cofactor specificity remains elusive. In this study, we will work alongside experimental collaborators to increase understanding of fundamental features which influence promiscuity of Rossmann Fold MTases to various nucleotides.