PDBsum entry 2c19

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protein metals Protein-protein interface(s) links
Lyase PDB id
Protein chains
334 a.a. *
_NA ×2
_MG ×2
Waters ×659
* Residue conservation analysis
PDB id:
Name: Lyase
Title: 5-(4-carboxy-2-oxo-butylsulfanyl)-4-oxo-pentanoic acid acid bound to porphobilinogen synthase from pseudomonas aeruginosa
Structure: Delta-aminolevulinic acid dehydratase. Chain: a, b,. Synonym: porphobilinogen synthase, alad, aladh. Engineered: yes
Source: Pseudomonas aeruginosa. Organism_taxid: 287. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Octamer (from PDB file)
2.05Å     R-factor:   0.147     R-free:   0.201
Authors: F.Frere,M.Nentwich,S.Gacond,D.W.Heinz,R.Neier, N.Frankenberg-Dinkel
Key ref: F.Frère et al. (2006). Probing the active site of Pseudomonas aeruginosa porphobilinogen synthase using newly developed inhibitors. Biochemistry, 45, 8243-8253. PubMed id: 16819823 DOI: 10.1021/bi052611f
11-Sep-05     Release date:   20-Jun-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q59643  (HEM2_PSEAE) -  Delta-aminolevulinic acid dehydratase
337 a.a.
334 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

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

Porphyrin Biosynthesis (early stages)
      Reaction: 2 5-aminolevulinate = porphobilinogen + 2 H2O
2 × 5-aminolevulinate
= porphobilinogen
+ 2 × H(2)O
      Cofactor: Zn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     tetrapyrrole biosynthetic process   4 terms 
  Biochemical function     catalytic activity     4 terms  


    Added reference    
DOI no: 10.1021/bi052611f Biochemistry 45:8243-8253 (2006)
PubMed id: 16819823  
Probing the active site of Pseudomonas aeruginosa porphobilinogen synthase using newly developed inhibitors.
F.Frère, M.Nentwich, S.Gacond, D.W.Heinz, R.Neier, N.Frankenberg-Dinkel.
Porphobilinogen synthase catalyzes the first committed step of the tetrapyrrole biosynthesis pathway. In an aldol-like condensation, two molecules of 5-aminolevulinic acid (ALA) form the first pyrrole, porphobilinogen. Newly synthesized analogues of a reaction intermediate of porphobilinogen synthase have been employed in studying the active site and the catalytic mechanism of this early enzyme of tetrapyrrole biosynthesis. This study combines structural and kinetic evaluation of the inhibition potency of these inhibitors. In addition, one of the determined protein structures provides for the first time structural evidence of a magnesium ion in the active site. From these results, we can corroborate an earlier postulated enzymatic mechanism that starts with formation of a C-C bond, linking C3 of the A-side ALA to C4 of the P-side ALA through an aldole addition. The obtained data are discussed with respect to the current literature.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21514151 N.Iwai, K.Nakayama, J.Oku, and T.Kitazume (2011).
Synthesis and antibacterial activity of alaremycin derivatives for the porphobilinogen synthase.
  Bioorg Med Chem Lett, 21, 2812-2815.  
20506125 G.Layer, J.Reichelt, D.Jahn, and D.W.Heinz (2010).
Structure and function of enzymes in heme biosynthesis.
  Protein Sci, 19, 1137-1161.  
19822707 I.U.Heinemann, C.Schulz, W.D.Schubert, D.W.Heinz, Y.G.Wang, Y.Kobayashi, Y.Awa, M.Wachi, D.Jahn, and M.Jahn (2010).
Structure of the heme biosynthetic Pseudomonas aeruginosa porphobilinogen synthase in complex with the antibiotic alaremycin.
  Antimicrob Agents Chemother, 54, 267-272.
PDB code: 2woq
17311232 S.Gacond, F.Frère, M.Nentwich, J.P.Faurite, N.Frankenberg-Dinkel, and R.Neier (2007).
Synthesis of bisubstrate inhibitors of porphobilinogen synthase from Pseudomonas aeruginosa.
  Chem Biodivers, 4, 189-202.  
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