A cytosine modification mechanism revealed by the structure of a ternary complex of deoxycytidylate hydroxymethylase from bacteriophage T4 with its cofactor and substrate.

ABSTRACT: To protect viral DNA against the host bacterial restriction system, bacterio-phages utilize a special modification system - hydroxymethylation - in which dCMP hydroxymethylase (dCH) converts dCMP to 5-hydroxymethyl-dCMP (5hm-dCMP) using N5,N10-methylenetetrahydrofolate as a cofactor. Despite shared similarity with thymidylate synthase (TS), dCH catalyzes hydroxylation through an exocyclic methylene intermediate during the last step, which is different from the hydride transfer that occurs with TS. In contrast to the extensively studied TS, the hydroxymethylation mechanism of a cytosine base is not well understood due to the lack of a ternary complex structure of dCH in the presence of both its substrate and cofactor. This paper reports the crystal structure of the ternary com

SUBMITTER: Park SH 

PROVIDER: S-EPMC6400193 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature