An engineered variant of SETD3 methyltransferase alters target specificity from histidine to lysine methylation.

ABSTRACT: Most characterized SET domain (SETD) proteins are protein lysine methyltransferases, but SETD3 was recently demonstrated to be a protein (i.e. actin) histidine-N₃ methyltransferase. Human SETD3 shares a high structural homology with two known protein lysine methyltransferases-human SETD6 and the plant LSMT-but differs in the residues constituting the active site. In the SETD3 active site, Asn²⁵⁵ engages in a unique hydrogen-bonding interaction with the target histidine of actin that likely contributes to its >1300-fold greater catalytic efficiency (k_cat/K_m ) on histidine than on lysine. Here, we engineered active-site variants to switch the SETD3 target specificity from histidine to lysine. Substitution of Asn²⁵⁵ w

SUBMITTER: Dai S 

PROVIDER: S-EPMC7049955 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature