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PDBsum entry 1s5v

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protein links
Lyase PDB id
1s5v
Jmol
Contents
Protein chains
292 a.a. *
Waters ×231
* Residue conservation analysis
PDB id:
1s5v
Name: Lyase
Title: Crystal structure analysis of a mutant of dihydrodipicolinat synthase--residue tyr107 to phe107
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.
Resolution:
2.35Å     R-factor:   0.197     R-free:   0.232
Authors: R.C.J.Dobson,K.Valegard,J.A.Gerrard
Key ref:
R.C.Dobson et al. (2004). The crystal structure of three site-directed mutants of Escherichia coli dihydrodipicolinate synthase: further evidence for a catalytic triad. J Mol Biol, 338, 329-339. PubMed id: 15066435 DOI: 10.1016/j.jmb.2004.02.060
Date:
21-Jan-04     Release date:   27-Apr-04    
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     5 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.jmb.2004.02.060 J Mol Biol 338:329-339 (2004)
PubMed id: 15066435  
 
 
The crystal structure of three site-directed mutants of Escherichia coli dihydrodipicolinate synthase: further evidence for a catalytic triad.
R.C.Dobson, K.Valegård, J.A.Gerrard.
 
  ABSTRACT  
 
Dihydrodipicolinate synthase (DHDPS, EC 4.2.1.52) catalyses the branchpoint reaction of lysine biosynthesis in plants and microbes: the condensation of (S)-aspartate-beta-semialdehyde and pyruvate. The crystal structure of wild-type DHDPS has been published to 2.5A, revealing a tetrameric molecule comprised of four identical (beta/alpha)(8)-barrels, each containing one active site. Previous workers have hypothesised that the catalytic mechanism of the enzyme involves a catalytic triad of amino acid residues, Tyr133, Thr44 and Tyr107, which provide a proton shuttle to transport protons from the active site to solvent. We have tested this hypothesis using site-directed mutagenesis to produce three mutant enzymes: DHDPS-Y133F, DHDPS-T44V and DHDPS-Y107F. Each of these mutants has substantially reduced activity, consistent with the catalytic triad hypothesis. We have determined each mutant crystal structure to at least 2.35A resolution and compared the structures to the wild-type enzyme. All mutant enzymes crystallised in the same space group as the wild-type form and only minor differences in structure are observed. These results suggest that the catalytic triad is indeed in operation in wild-type DHDPS.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Putative roles for the catalytic triad in the mechanism of DHDPS. This mechanism has been adapted from Hutton et al.[33.]
Figure 5.
Figure 5. Stereo-view showing overlays of the active sites of wild-type (black) and mutant DHDPS structures (gold). Electron density covers the mutated residue in each image and is contoured to 1s. Shown from top to bottom: a, DHDPS-Y133F; b, DHDPS-T44V; c, DHDPS-Y107F. The images were generated using O[31.] and Molray. [35.]
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 338, 329-339) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20122228 A.Garg, R.Tewari, and G.P.Raghava (2010).
Virtual Screening of potential drug-like inhibitors against Lysine/DAP pathway of Mycobacterium tuberculosis.
  BMC Bioinformatics, 11, S53.  
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
19225662 S.R.Devenish, and J.A.Gerrard (2009).
The role of quaternary structure in (beta/alpha)(8)-barrel proteins: evolutionary happenstance or a higher level of structure-function relationships?
  Org Biomol Chem, 7, 833-839.  
  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.  
16287120 E.Blagova, V.Levdikov, N.Milioti, M.J.Fogg, A.K.Kalliomaa, J.A.Brannigan, K.S.Wilson, and A.J.Wilkinson (2006).
Crystal structure of dihydrodipicolinate synthase (BA3935) from Bacillus anthracis at 1.94 A resolution.
  Proteins, 62, 297-301.
PDB codes: 1xky 1xl9
16525757 R.A.Azevedo, M.Lancien, and P.J.Lea (2006).
The aspartic acid metabolic pathway, an exciting and essential pathway in plants.
  Amino Acids, 30, 143-162.  
16950779 S.Watanabe, N.Shimada, K.Tajima, T.Kodaki, and K.Makino (2006).
Identification and characterization of L-arabonate dehydratase, L-2-keto-3-deoxyarabonate dehydratase, and L-arabinolactonase involved in an alternative pathway of L-arabinose metabolism. Novel evolutionary insight into sugar metabolism.
  J Biol Chem, 281, 33521-33536.  
15981001 M.A.Perugini, M.D.Griffin, B.J.Smith, L.E.Webb, A.J.Davis, E.Handman, and J.A.Gerrard (2005).
Insight into the self-association of key enzymes from pathogenic species.
  Eur Biophys J, 34, 469-476.  
16041077 R.C.Dobson, M.D.Griffin, G.B.Jameson, and J.A.Gerrard (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.
PDB codes: 1yxc 1yxd
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.