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Cloning and characterisation of dihydrodipicolinate synthase from the pathogen Neisseria meningitidis

DOI: 10.1016/j.bbapap.2009.02.003 DOI Help
PMID: 19236959 PMID Help

Authors: Sean R. A. Devenish (University of Canterbury (New Zealand)) , Frances H. A. Huisman (University of Canterbury (New Zealand)) , Emily J. Parker (University of Canterbury (New Zealand)) , Andrea T. Hadfield (University of Bristol) , Juliet A. Gerrard (University of Canterbury (New Zealand))
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochimica Et Biophysica Acta (bba) - Proteins And Proteomics , VOL 1794 (8) , PAGES 1168-74

State: Published (Approved)
Published: August 2009

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.

Journal Keywords: Cloning; Molecular; Crystallography; X-Ray; Enzyme; Escherichia; Hydro-Lyases; Hydrogen; Kinetics; Neisseria; Protein Multimerization

Diamond Keywords: Bacteria; Meningitis; Enzymes

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Instruments: I02-Macromolecular Crystallography

Added On: 03/08/2009 10:43

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Biochemistry Chemistry Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)