Structure of Escherichia coli tetrahydrodipicolinate N-succinyltransferase reveals the role of a conserved C-terminal helix in cooperative substrate binding

Abstract 

Tetrahydrodipicolinate N-succinyltransferase is an enzyme present in many bacteria that catalyzes the first step of the succinylase pathway for the synthesis of meso-diaminopimelate and the amino acid l-lysine. Inhibition of the synthesis of meso-diaminopimelate, a component of peptidoglycan present in the cell wall of bacteria, is a potential route for the development of novel anti-bacterial agents. Here, we report the crystal structure of the DapD tetrahydrodipicolinate N-succinyltransferase from Escherichia coli at 2.0Å resolution. Comparison of the structure with the homologous enzyme from Mycobacterium bovis reveals the C-terminal helix undergoes a large rearrangement upon substrate binding, which contributes to cooperativity in substrate binding.

Keywords: Protein structure, Succinyltransferase, THDP, DapD, Lysine biosynthesis, X-ray crystallography

Abbreviations: THDP, 2,3,4,5-tetrahydrodipicolinate, DAP, diaminopimelate, LβH, left-handed parallel β-helix, CoA, coenzyme A, Tris, tris(hydroxymethyl)aminomethane