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PDBsum entry 2a6n

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protein metals Protein-protein interface(s) links
Lyase PDB id
2a6n
Jmol
Contents
Protein chains
292 a.a. *
Metals
__K ×2
Waters ×596
* Residue conservation analysis
PDB id:
2a6n
Name: Lyase
Title: Dihydrodipicolinate synthase (e. Coli)- mutant r138a
Structure: Dihydrodipicolinate synthase. Chain: a, b. Synonym: dhdps. Engineered: yes. Mutation: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: dapa. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
Resolution:
1.94Å     R-factor:   0.164     R-free:   0.191
Authors: R.C.Dobson,S.R.Devenish,L.A.Turner,V.R.Clifford,F.G.Pearce, G.B.Jameson,J.A.Gerrard
Key ref:
R.C.Dobson et al. (2005). Role of arginine 138 in the catalysis and regulation of Escherichia coli dihydrodipicolinate synthase. Biochemistry, 44, 13007-13013. PubMed id: 16185069 DOI: 10.1021/bi051281w
Date:
03-Jul-05     Release date:   18-Oct-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0A6L2  (DAPA_ECOLI) -  4-hydroxy-tetrahydrodipicolinate synthase
Seq:
Struc:
292 a.a.
292 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.4.3.3.7  - 4-hydroxy-tetrahydrodipicolinate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Pyruvate + L-aspartate-4-semialdehyde = (4S)-4-hydroxy-2,3,4,5- tetrahydro-(2S)-dipicolinate + H2O
Pyruvate
+ L-aspartate-4-semialdehyde
= (4S)-4-hydroxy-2,3,4,5- tetrahydro-(2S)-dipicolinate
+ 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   5 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/bi051281w Biochemistry 44:13007-13013 (2005)
PubMed id: 16185069  
 
 
Role of arginine 138 in the catalysis and regulation of Escherichia coli dihydrodipicolinate synthase.
R.C.Dobson, S.R.Devenish, L.A.Turner, V.R.Clifford, F.G.Pearce, G.B.Jameson, J.A.Gerrard.
 
  ABSTRACT  
 
In plants and bacteria, the branch point of (S)-lysine biosynthesis is the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate, a reaction catalyzed by dihydrodipicolinate synthase (DHDPS, EC 4.2.1.52). It has been proposed that Arg138, a residue situated at the entrance to the active site of DHDPS, is responsible for binding the carboxyl of (S)-ASA and may additionally be involved in the mechanism of (S)-lysine inhibition. This study tests these assertions by mutation of Arg138 to both histidine and alanine. Following purification, DHDPS-R138H and DHDPS-R138A each showed severely compromised activity (approximately 0.1% that of the wild type), and the apparent Michaelis-Menten constant for (S)-ASA in each mutant, calculated using a pseudo-single substrate analysis, was significantly higher than that of the wild type. This provides good evidence that Arg138 is indeed essential for catalysis and plays a key role in substrate binding. To test whether structural changes could account for the change in kinetic behavior, the solution structure was probed via far-UV circular dichroism, confirming that the mutations at position 138 did not modify secondary structure. The crystal structures of both mutant enzymes were determined, confirming the presence of the mutations and suggesting that Arg138 plays an important role in catalysis: the stabilization of the catalytic triad residues, a motif we have previously demonstrated to be essential for activity. In addition, the role of Arg138 in (S)-lysine inhibition was examined. Both mutant enzymes showed the same IC(50) values as the wild type but different partial inhibition patterns, from which it is concluded that arginine 138 is not essential for (S)-lysine inhibition.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  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.  
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
  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.  
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.