Structural insights for the substrate recognition mechanism of LL-diaminopimelate aminotransferase

The enzymes involved in the lysine biosynthetic pathway have long been considered to be attractive targets for novel antibiotics due to the absence of this pathway in humans. Recently, a novel pyridoxal 5′-phosphate (PLP) dependent enzyme called ll-diaminopimelate aminotransferase (ll-DAP-AT) was identified in the lysine biosynthetic pathway of plants and Chlamydiae. Understanding its function and substrate recognition mechanism would be an important initial step toward designing novel antibiotics targeting ll-DAP-AT. The crystal structures of ll-DAP-AT from Arabidopsis thaliana in complex with various substrates and analogues have been solved recently. These structures revealed how l-glutamate and ll-DAP are recognized by ll-DAP-AT without significant conformational changes in the enzyme's backbone structure. This review article summarizes the recent developments in the structural characterization and the inhibitor design of ll-DAP-AT from A. thaliana. This article is part of a Special Issue entitled: Pyridoxal Phospate Enzymology.

► We reviewed the recent advances in ll-DAP-AT research.
► We summarized the recent structural work in ll-DAP-AT.
► We illustrated the substrate binding mode of ll-DAP-AT.