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

FEBS Lett. 2008 Mar 5;582(5):623-6. doi: 10.1016/j.febslet.2008.01.032. Epub 2008 Jan 31.

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 2.0 A 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acyltransferases / chemistry*
  • Acyltransferases / metabolism*
  • Amino Acid Sequence
  • Conserved Sequence*
  • Crystallography, X-Ray
  • Escherichia coli / enzymology*
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Acyltransferases
  • succinyl-CoA-tetrahydrodipicolinate N-succinyltransferase

Associated data

  • PDB/3BXY