Structure of 2C-methyl-D-erythritol 2,4- cyclodiphosphate synthase: an essential enzyme for isoprenoid biosynthesis and target for antimicrobial drug development.

ABSTRACT: The crystal structure of the zinc enzyme Escherichia coli 2C-methyl-d-erythritol 2,4-cyclodiphosphate synthase in complex with cytidine 5'-diphosphate and Mn(2+) has been determined to 1.8-A resolution. This enzyme is essential in E. coli and participates in the nonmevalonate pathway of isoprenoid biosynthesis, a critical pathway present in some bacterial and apicomplexans but distinct from that used by mammals. Our analysis reveals a homotrimer, built around a beta prism, carrying three active sites, each of which is formed in a cleft between pairs of subunits. Residues from two subunits recognize and bind the nucleotide in an active site that contains a Zn(2+) with tetrahedral coordination. A Mn(2+), with octahedral geometry, is positioned between the alpha and beta phosphates acting in

SUBMITTER: Kemp LE 

PROVIDER: S-EPMC124447 | biostudies-literature | 2002 May

REPOSITORIES: biostudies-literature