Atomic-Resolution 1.3 Å Crystal Structure, Inhibition by Sulfate, and Molecular Dynamics of the Bacterial Enzyme DapE

We report the atomic-resolution (1.3 Å) X-ray crystal structure of an open conformation dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE, EC 3.5.1.18) from Neisseria meningitidis. This [Protein Data Bank (PDB) entry 5UEJ] contains two bound sulfate ions in active site that mimic binding terminal carboxylates (l,l-SDAP) substrate. demonstrated inhibition DapE by (IC50 = 13.8 ± 2.8 mM). Comparison with other structures PDB demonstrates flexibility interdomain connections this protein. high-resolution was then utilized as starting point for targeted molecular dynamics experiments revealing conformational change form to closed occurs when binds l,l-SDAP and cleaves amide bond. These simulations closure conformation, RMS throughout closure, independence movement subunits. occurred phases catalytic domains moving toward dimerization first, followed a rotation relative domains. Although there were no targeting forces, substrate moved closer more tightly during event.