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Cloning and characterisation of dihydrodipicolinate synthase from the pathogen Neisseria meningitidis
DOI:
10.1016/j.bbapap.2009.02.003
PMID:
19236959
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)