Examining prestructured β-actin peptides as substrates of histidine methyltransferase SETD3.

ABSTRACT: The N^τ-His73 methylation of β-actin by histidine methyltransferase SETD3 is required for the integrity of the cellular cytoskeleton. Modulation of SETD3 activity in human cells facilitates cancer-like changes to the cell phenotype. SETD3 binds β-actin in an extended conformation, with a conserved bend-like motif surrounding His73. Here, we report on the catalytic specificity of SETD3 towards i, i + 3 stapled β-actin peptides possessing a limited conformational freedom surrounding the His73 substrate residue via positions Glu72 and Ile75. Stapled β-actin peptides were observed to be methylated less efficiently than the linear β-actin peptide. None of the stapled β-actin peptides efficiently inhibited the SETD3-catalyzed N^τ-His73 methylation reaction. Molecular dynamics

SUBMITTER: Maas MN 

PROVIDER: S-EPMC11531485 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature