SMYD proteins are an exciting field of study as they are linked to many types of cancer- related pathways. Cardiac and skeletal muscle development and function also depend on SMYD proteins opening a possible avenue for cardiac-related treatment. Previous crystal structure studies have revealed that this special class of protein lysine methyltransferases have a bilobal structure, and an open–closed motion may regulate substrate specificity. Here we use the molecular dynamics simulation to investigate the still-poorly-understood SMYD2 dynamics. Cross-correlation analysis reveals that SMYD2 exhibits a negative cor- related inter-lobe motion. Principle component analysis suggests that this correlated dynamic is contributed to by a twisting motion of the C-lobe with respect to the N-lobe and a clamshell-like motion between the lobes. Dynamical network analysis defines possible allo- steric paths for the correlated dynamics. There are nine communities in the dynamical net- work with six in the N-lobe and three in the C-lobe, and the communication between the lobes is mediated by a lobe-bridging β hairpin. This study provides insight into the dynam- ical nature of SMYD2 and could facilitate better understanding of SMYD2 substrate specificity.
Biochemistry | Molecular Biology
Spellmon N, Sun X, Sirinupong N, Edwards B, Li C, Yang Z (2015) Molecular Dynamics Simulation Reveals Correlated Inter-Lobe Motion in Protein Lysine Methyltransferase SMYD2. PLoS ONE 10(12): e0145758. doi:10.1371/journal.pone.0145758