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Lyase PDB id
1yxd
Jmol
Contents
Protein chains
292 a.a. *
Ligands
LYS ×3
Metals
_CL ×2
__K ×2
Waters ×557
* Residue conservation analysis
PDB id:
1yxd
Name: Lyase
Title: Structure of e. Coli dihydrodipicolinate synthase bound with allosteric inhibitor (s)-lysine to 2.0 a
Structure: Dihydrodipicolinate synthase. Chain: a, b. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: dapa. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
Resolution:
2.00Å     R-factor:   0.161     R-free:   0.186
Authors: R.C.J.Dobson,M.D.W.Griffin,G.B.Jameson,J.A.Gerrard
Key ref:
R.C.Dobson et al. (2005). The crystal structures of native and (S)-lysine-bound dihydrodipicolinate synthase from Escherichia coli with improved resolution show new features of biological significance. Acta Crystallogr D Biol Crystallogr, 61, 1116-1124. PubMed id: 16041077 DOI: 10.1107/S0907444905016318
Date:
20-Feb-05     Release date:   02-Aug-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0A6L2  (DAPA_ECOLI) -  Dihydrodipicolinate synthase
Seq:
Struc: 		292 a.a.
292 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.2.1.52  - Dihydrodipicolinate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Lysine biosynthesis (early stages)
      Reaction: L-aspartate 4-semialdehyde + pyruvate = dihydrodipicolinate + 2 H2O
L-aspartate 4-semialdehyde
 + pyruvate
 =
dihydrodipicolinate
Bound ligand (Het Group name = LYS)
matches with 69.00% similarity 		+ 2 × H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1107/S0907444905016318 Acta Crystallogr D Biol Crystallogr 61:1116-1124 (2005)
PubMed id: 16041077  
 
 
The crystal structures of native and (S)-lysine-bound dihydrodipicolinate synthase from Escherichia coli with improved resolution show new features of biological significance.
R.C.Dobson, M.D.Griffin, G.B.Jameson, J.A.Gerrard.
 
  ABSTRACT  
 
Dihydrodipicolinate synthase (DHDPS) mediates the key first reaction common to the biosynthesis of (S)-lysine and meso-diaminopimelate. The activity of DHDPS is allosterically regulated by the feedback inhibitor (S)-lysine. The crystal structure of DHDPS from Escherichia coli has previously been published, but to only a resolution of 2.5 A, and the structure of the lysine-bound adduct was known to only 2.94 A resolution. Here, the crystal structures of native and (S)-lysine-bound dihydrodipicolinate synthase from E. coli are presented to 1.9 and 2.0 A, respectively, resolutions that allow, in particular, more accurate definition of the protein structure. The general architecture of the active site is found to be consistent with previously determined structures, but with some important differences. Arg138, which is situated at the entrance of the active site and is thought to be involved in substrate binding, has an altered conformation and is connected via a water molecule to Tyr133 of the active-site catalytic triad. This suggests a hitherto unknown function for Arg138 in the DHDPS mechanism. Additionally, a re-evaluation of the dimer-dimer interface reveals a more extensive network of interactions than first thought. Of particular interest is the higher resolution structure of DHDPS with (S)-lysine bound at the allosteric site, which is remote to the active site, although connected to it by a chain of conserved water molecules. (S)-Lysine has a slightly altered conformation from that originally determined and does not appear to alter the DHDPS structure as others have reported.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 Currently accepted mechanism of DHDPS. 		Figure 3.
Figure 3 Tertiary and quaternary structure of DHDPS. (a) View looking down the ( [beta] / [alpha] )[8]-barrel and C-terminal domain. The active site is defined by the position of Lys161 (stick view). (b) Side view of the ( [beta] / [alpha] )[8]-barrel and C-terminal domain. (c) The quaternary structure. Monomers A and B make up the asymmetric unit. This and subsequent figures were produced using PyMOL (DeLano, 2002 [DeLano, W. L. (2002). The PyMOL Molecular Graphics System. DeLano Scientific, San Carlos, CA, USA. http://www.pymol.org .]-[bluearr.gif] ) unless stated otherwise.
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2005, 61, 1116-1124) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19948665 J.E.Voss, S.W.Scally, N.L.Taylor, S.C.Atkinson, M.D.Griffin, C.A.Hutton, M.W.Parker, M.R.Alderton, J.A.Gerrard, R.C.Dobson, C.Dogovski, and M.A.Perugini (2010).
Substrate-mediated stabilization of a tetrameric drug target reveals Achilles heel in anthrax.
  J Biol Chem, 285, 5188-5195.
PDB code: 3hij
  19194017 J.E.Voss, S.W.Scally, N.L.Taylor, C.Dogovski, M.R.Alderton, C.A.Hutton, J.A.Gerrard, M.W.Parker, R.C.Dobson, and M.A.Perugini (2009).
Expression, purification, crystallization and preliminary X-ray diffraction analysis of dihydrodipicolinate synthase from Bacillus anthracis in the presence of pyruvate.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 188-191.  
  19255476 S.C.Atkinson, R.C.Dobson, J.M.Newman, M.A.Gorman, C.Dogovski, M.W.Parker, and M.A.Perugini (2009).
Crystallization and preliminary X-ray analysis of dihydrodipicolinate synthase from Clostridium botulinum in the presence of its substrate pyruvate.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 253-255.  
  18607102 B.R.Burgess, R.C.Dobson, C.Dogovski, G.B.Jameson, M.W.Parker, and M.A.Perugini (2008).
Purification, crystallization and preliminary X-ray diffraction studies to near-atomic resolution of dihydrodipicolinate synthase from methicillin-resistant Staphylococcus aureus.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 659-661.  
18684709 B.R.Burgess, R.C.Dobson, M.F.Bailey, S.C.Atkinson, M.D.Griffin, G.B.Jameson, M.W.Parker, J.A.Gerrard, and M.A.Perugini (2008).
Structure and evolution of a novel dimeric enzyme from a clinically important bacterial pathogen.
  J Biol Chem, 283, 27598-27603.
PDB code: 3daq
18536061 C.P.Phenix, K.Nienaber, P.H.Tam, L.T.Delbaere, and D.R.Palmer (2008).
Structural, functional and calorimetric investigation of MosA, a dihydrodipicolinate synthase from Sinorhizobium meliloti l5-30, does not support involvement in rhizopine biosynthesis.
  Chembiochem, 9, 1591-1602.
PDB code: 2vc6
18787203 R.C.Dobson, M.D.Griffin, S.R.Devenish, F.G.Pearce, C.A.Hutton, J.A.Gerrard, G.B.Jameson, and M.A.Perugini (2008).
Conserved main-chain peptide distortions: a proposed role for Ile203 in catalysis by dihydrodipicolinate synthase.
  Protein Sci, 17, 2080-2090.
PDB code: 3c0j
  18323610 R.C.Dobson, S.C.Atkinson, M.A.Gorman, J.M.Newman, M.W.Parker, and M.A.Perugini (2008).
The purification, crystallization and preliminary X-ray diffraction analysis of dihydrodipicolinate synthase from Clostridium botulinum.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 206-208.  
  19052357 S.R.Devenish, J.A.Gerrard, G.B.Jameson, and R.C.Dobson (2008).
The high-resolution structure of dihydrodipicolinate synthase from Escherichia coli bound to its first substrate, pyruvate.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1092-1095.  
18340401 S.Wolterink-van Loo, M.Levisson, M.C.Cabrières, M.C.Franssen, and J.van der Oost (2008).
Characterization of a thermostable dihydrodipicolinate synthase from Thermoanaerobacter tengcongensis.
  Extremophiles, 12, 461-469.  
17579770 C.A.Hutton, M.A.Perugini, and J.A.Gerrard (2007).
Inhibition of lysine biosynthesis: an evolving antibiotic strategy.
  Mol Biosyst, 3, 458-465.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.