3FLU

Crystal structure of dihydrodipicolinate synthase from the pathogen Neisseria meningitidis

Summary for 3FLU

• Entry DOI: 10.2210/pdb3flu/pdb
• Related: 1YXC 1YXD
• Descriptor: Dihydrodipicolinate synthase, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: tim barrel, beta-alpha-barrel, amino-acid biosynthesis, diaminopimelate biosynthesis, lyase, lysine biosynthesis, schiff base
• Biological source: Neisseria meningitidis serogroup B
• Cellular location: Cytoplasm : Q9JZR4
• Total number of polymer chains: 4
• Total formula weight: 130559.97

Authors

Devenish, S.R.A.,Hadfield, A.T. (deposition date: 2008-12-19, release date: 2009-06-23, Last modification date: 2023-11-01)

Primary citation

Devenish, S.R.A.,Huisman, F.H.A.,Parker, E.J.,Hadfield, A.T.,Gerrard, J.A.
Cloning and characterisation of dihydrodipicolinate synthase from the pathogen Neisseria meningitidis.
Biochim.Biophys.Acta, 2009

PubMed Abstract: Neisseria meningitidis is an obligate commensal bacterium of humans, and also an important human pathogen. To facilitate future drug studies, we report here the biochemical and structural characterisation of a key enzyme in (S)-lysine biosynthesis, dihydrodipicolinate synthase (DHDPS), from N. meningitidis (NmeDHDPS). X-ray crystallography revealed only minor structural differences between NmeDHDPS and the enzyme from E. coli at the active and allosteric effector sites. The catalytic capabilities of NmeDHDPS are similar to those of the enzyme from E. coli, but intriguingly NmeDHDPS is subject to substrate inhibition by high concentrations of the second substrate, (S)-aspartate semialdehyde, and is also significantly more sensitive to feedback inhibition by (S)-lysine. This heightened sensitivity to inhibition at both active and allosteric sites suggests that it may be possible to target DHDPS from N. meningitidis for antibiotic development.

PubMed: 19236959
DOI: 10.1016/j.bbapap.2009.02.003

Experimental method

X-RAY DIFFRACTION (2 Å)