3FLU

Crystal structure of dihydrodipicolinate synthase from the pathogen Neisseria meningitidis

PDB DOI: https://doi.org/10.2210/pdb3FLU/pdb

Classification: LYASE
Organism(s): Neisseria meningitidis serogroup B
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2008-12-19 Released: 2009-06-23
Deposition Author(s): Devenish, S.R.A., Hadfield, A.T.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.191
R-Value Work: 0.148
R-Value Observed: 0.151

wwPDB Validation 3D Report Full Report

This is version 1.3 of the entry. See complete history.

Literature

Cloning and characterisation of dihydrodipicolinate synthase from the pathogen Neisseria meningitidis.

Devenish, S.R.A., Huisman, F.H.A., Parker, E.J., Hadfield, A.T., Gerrard, J.A.

(2009) Biochim Biophys Acta

PubMed: 19236959 Search on PubMed
DOI: https://doi.org/10.1016/j.bbapap.2009.02.003
Primary Citation of Related Structures:
3FLU

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.

Organizational Affiliation

School of Biological Sciences, University of Canterbury, Christchurch, New Zealand. sean.devenish@canterbury.ac.nz

Macromolecule Content

Total Structure Weight: 130.56 kDa
Atom Count: 10,062
Modelled Residue Count: 1,170
Deposited Residue Count: 1,188
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Dihydrodipicolinate synthase	A, B, C, D	297	Neisseria meningitidis serogroup B	Mutation(s): 0 Gene Names: dapA, NMB0929 EC: 4.2.1.52
UniProt
Find proteins for Q9JZR4 (Neisseria meningitidis serogroup B (strain MC58)) Explore Q9JZR4 Go to UniProtKB: Q9JZR4
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9JZR4
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain AA [auth C] SDF format, chain BA [auth C] SDF format, chain CA [auth C] SDF format, chain DA [auth C] SDF format, chain E [auth A] SDF format, chain EA [auth C] SDF format, chain F [auth A] SDF format, chain FA [auth C] SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain OA [auth D] SDF format, chain PA [auth D] SDF format, chain Q [auth B] SDF format, chain QA [auth D] SDF format, chain R [auth B] SDF format, chain S [auth B] SDF format, chain T [auth B] MOL2 format, chain AA [auth C] MOL2 format, chain BA [auth C] MOL2 format, chain CA [auth C] MOL2 format, chain DA [auth C] MOL2 format, chain E [auth A] MOL2 format, chain EA [auth C] MOL2 format, chain F [auth A] MOL2 format, chain FA [auth C] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain OA [auth D] MOL2 format, chain PA [auth D] MOL2 format, chain Q [auth B] MOL2 format, chain QA [auth D] MOL2 format, chain R [auth B] MOL2 format, chain S [auth B] MOL2 format, chain T [auth B]	AA [auth C] BA [auth C] CA [auth C] DA [auth C] E [auth A] AA [auth C], BA [auth C], CA [auth C], DA [auth C], E [auth A], EA [auth C], F [auth A], FA [auth C], G [auth A], H [auth A], I [auth A], OA [auth D], PA [auth D], Q [auth B], QA [auth D], R [auth B], S [auth B], T [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain AA [auth C] Focus chain BA [auth C] Focus chain CA [auth C] Focus chain DA [auth C] Focus chain E [auth A] Focus chain EA [auth C] Focus chain F [auth A] Focus chain FA [auth C] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain OA [auth D] Focus chain PA [auth D] Focus chain Q [auth B] Focus chain QA [auth D] Focus chain R [auth B] Focus chain S [auth B] Focus chain T [auth B] Interactions & Density Focus chain AA [auth C] Focus chain BA [auth C] Focus chain CA [auth C] Focus chain DA [auth C] Focus chain E [auth A] Focus chain EA [auth C] Focus chain F [auth A] Focus chain FA [auth C] Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain OA [auth D] Focus chain PA [auth D] Focus chain Q [auth B] Focus chain QA [auth D] Focus chain R [auth B] Focus chain S [auth B] Focus chain T [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain GA [auth C] SDF format, chain HA [auth C] SDF format, chain IA [auth C] SDF format, chain J [auth A] SDF format, chain JA [auth C] SDF format, chain K [auth A] SDF format, chain KA [auth C] SDF format, chain L [auth A] SDF format, chain LA [auth C] SDF format, chain M [auth A] SDF format, chain MA [auth C] SDF format, chain N [auth A] SDF format, chain NA [auth C] SDF format, chain O [auth A] SDF format, chain P [auth A] SDF format, chain RA [auth D] SDF format, chain SA [auth D] SDF format, chain TA [auth D] SDF format, chain U [auth B] SDF format, chain UA [auth D] SDF format, chain V [auth B] SDF format, chain VA [auth D] SDF format, chain W [auth B] SDF format, chain WA [auth D] SDF format, chain X [auth B] SDF format, chain XA [auth D] SDF format, chain Y [auth B] SDF format, chain YA [auth D] SDF format, chain Z [auth B] MOL2 format, chain GA [auth C] MOL2 format, chain HA [auth C] MOL2 format, chain IA [auth C] MOL2 format, chain J [auth A] MOL2 format, chain JA [auth C] MOL2 format, chain K [auth A] MOL2 format, chain KA [auth C] MOL2 format, chain L [auth A] MOL2 format, chain LA [auth C] MOL2 format, chain M [auth A] MOL2 format, chain MA [auth C] MOL2 format, chain N [auth A] MOL2 format, chain NA [auth C] MOL2 format, chain O [auth A] MOL2 format, chain P [auth A] MOL2 format, chain RA [auth D] MOL2 format, chain SA [auth D] MOL2 format, chain TA [auth D] MOL2 format, chain U [auth B] MOL2 format, chain UA [auth D] MOL2 format, chain V [auth B] MOL2 format, chain VA [auth D] MOL2 format, chain W [auth B] MOL2 format, chain WA [auth D] MOL2 format, chain X [auth B] MOL2 format, chain XA [auth D] MOL2 format, chain Y [auth B] MOL2 format, chain YA [auth D] MOL2 format, chain Z [auth B]	GA [auth C] HA [auth C] IA [auth C] J [auth A] JA [auth C] GA [auth C], HA [auth C], IA [auth C], J [auth A], JA [auth C], K [auth A], KA [auth C], L [auth A], LA [auth C], M [auth A], MA [auth C], N [auth A], NA [auth C], O [auth A], P [auth A], RA [auth D], SA [auth D], TA [auth D], U [auth B], UA [auth D], V [auth B], VA [auth D], W [auth B], WA [auth D], X [auth B], XA [auth D], Y [auth B], YA [auth D], Z [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain GA [auth C] Focus chain HA [auth C] Focus chain IA [auth C] Focus chain J [auth A] Focus chain JA [auth C] Focus chain K [auth A] Focus chain KA [auth C] Focus chain L [auth A] Focus chain LA [auth C] Focus chain M [auth A] Focus chain MA [auth C] Focus chain N [auth A] Focus chain NA [auth C] Focus chain O [auth A] Focus chain P [auth A] Focus chain RA [auth D] Focus chain SA [auth D] Focus chain TA [auth D] Focus chain U [auth B] Focus chain UA [auth D] Focus chain V [auth B] Focus chain VA [auth D] Focus chain W [auth B] Focus chain WA [auth D] Focus chain X [auth B] Focus chain XA [auth D] Focus chain Y [auth B] Focus chain YA [auth D] Focus chain Z [auth B] Interactions & Density Focus chain GA [auth C] Focus chain HA [auth C] Focus chain IA [auth C] Focus chain J [auth A] Focus chain JA [auth C] Focus chain K [auth A] Focus chain KA [auth C] Focus chain L [auth A] Focus chain LA [auth C] Focus chain M [auth A] Focus chain MA [auth C] Focus chain N [auth A] Focus chain NA [auth C] Focus chain O [auth A] Focus chain P [auth A] Focus chain RA [auth D] Focus chain SA [auth D] Focus chain TA [auth D] Focus chain U [auth B] Focus chain UA [auth D] Focus chain V [auth B] Focus chain VA [auth D] Focus chain W [auth B] Focus chain WA [auth D] Focus chain X [auth B] Focus chain XA [auth D] Focus chain Y [auth B] Focus chain YA [auth D] Focus chain Z [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.00 Å
R-Value Free: 0.191
R-Value Work: 0.148
R-Value Observed: 0.151
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 80.667	α = 90
b = 115.684	β = 90
c = 132.122	γ = 90

Software Package:

Software Name	Purpose
SCALA	data scaling
PHASER	phasing
REFMAC	refinement
PDB_EXTRACT	data extraction
DNA	data collection
DENZO	data reduction
SCALEPACK	data scaling

Structure Validation

View Full Validation Report

Entry History

Deposition Data

Released Date: 2009-06-23

Deposition Author(s):

Devenish, S.R.A.

Hadfield, A.T.

Revision History (Full details and data files)

Version 1.0: 2009-06-23
Type: Initial release
Version 1.1: 2011-07-13
Changes: Non-polymer description, Version format compliance
Version 1.2: 2017-11-01
Changes: Refinement description
Version 1.3: 2023-11-01
Changes: Data collection, Database references, Derived calculations, Refinement description