Structural basis for the target specificity of actin histidine methyltransferase SETD3.

ABSTRACT: SETD3 is an actin histidine-N₃ methyltransferase, whereas other characterized SET-domain enzymes are protein lysine methyltransferases. We report that in a pre-reactive complex SETD3 binds the N₃-protonated form (N₃-H) of actin His73, and in a post-reactive product complex, SETD3 generates the methylated histidine in an N₁-protonated (N₁-H) and N₃-methylated form. During the reaction, the imidazole ring of His73 rotates ~105°, which shifts the proton from N₃ to N₁, thus ensuring that the target atom N₃ is deprotonated prior to the methyl transfer. Under the conditions optimized for lysine deprotonation, SETD3 has weak lysine methylation activity on an actin peptide in which the target His73 i

SUBMITTER: Dai S 

PROVIDER: S-EPMC6684798 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature