PDBsum entry 2woq

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Lyase/antibiotic PDB id
Protein chain
329 a.a. *
EPE ×2
PE5 ×4
_MG ×4
Waters ×176
* Residue conservation analysis
PDB id:
Name: Lyase/antibiotic
Title: Porphobilinogen synthase (hemb) in complex with 5-acetamido- 4-oxohexanoic acid (alaremycin 2)
Structure: Delta-aminolevulinic acid dehydratase. Chain: a. Synonym: porphobilinogen synthase, aladh, alad. Engineered: yes
Source: Pseudomonas aeruginosa. Organism_taxid: 287. Expressed in: escherichia coli. Expression_system_taxid: 511693.
1.75Å     R-factor:   0.147     R-free:   0.179
Authors: I.U.Heinemann,C.Schulz,W.-D.Schubert,D.W.Heinz,Y.-G.Wang,Y.K Y.Awa,M.Wachi,D.Jahn,M.Jahn
Key ref: I.U.Heinemann et al. (2010). Structure of the heme biosynthetic Pseudomonas aeruginosa porphobilinogen synthase in complex with the antibiotic alaremycin. Antimicrob Agents Chemother, 54, 267-272. PubMed id: 19822707
27-Jul-09     Release date:   27-Oct-09    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q59643  (HEM2_PSEAE) -  Delta-aminolevulinic acid dehydratase
337 a.a.
329 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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
Bound ligand (Het Group name = AYC)
matches with 61.54% similarity
= 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    
Antimicrob Agents Chemother 54:267-272 (2010)
PubMed id: 19822707  
Structure of the heme biosynthetic Pseudomonas aeruginosa porphobilinogen synthase in complex with the antibiotic alaremycin.
I.U.Heinemann, C.Schulz, W.D.Schubert, D.W.Heinz, Y.G.Wang, Y.Kobayashi, Y.Awa, M.Wachi, D.Jahn, M.Jahn.
The recently discovered antibacterial compound alaremycin, produced by Streptomyces sp. A012304, structurally closely resembles 5-aminolevulinic acid, the substrate of porphobilinogen synthase. During the initial steps of heme biosynthesis, two molecules of 5-aminolevulinic acid are asymmetrically condensed to porphobilinogen. Alaremycin was found to efficiently inhibit the growth of both Gram-negative and Gram-positive bacteria. Using the newly created heme-permeable strain Escherichia coli CSA1, we are able to uncouple heme biosynthesis from bacterial growth and demonstrate that alaremycin targets the heme biosynthetic pathway. Further studies focused on the activity of alaremycin against the opportunistic pathogenic bacterium Pseudomonas aeruginosa. The MIC of alaremycin was determined to be 12 mM. Alaremycin was identified as a direct inhibitor of recombinant purified P. aeruginosa porphobilinogen synthase and had a K(i) of 1.33 mM. To understand the molecular basis of alaremycin's antibiotic activity at the atomic level, the P. aeruginosa porphobilinogen synthase was cocrystallized with the alaremycin. At 1.75-A resolution, the crystal structure reveals that the antibiotic efficiently blocks the active site of porphobilinogen synthase. The antibiotic binds as a reduced derivative of 5-acetamido-4-oxo-5-hexenoic acid. The corresponding methyl group is, however, not coordinated by any amino acid residues of the active site, excluding its functional relevance for alaremycin inhibition. Alaremycin is covalently bound by the catalytically important active-site lysine residue 260 and is tightly coordinated by several active-site amino acids. Our data provide a solid structural basis to further improve the activity of alaremycin for rational drug design. Potential approaches are discussed.

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.  
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