PDBsum entry 1eb3

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Dehydratase PDB id
Protein chain
340 a.a. *
Waters ×402
* Residue conservation analysis
PDB id:
Name: Dehydratase
Title: Yeast 5-aminolaevulinic acid dehydratase 4,7-dioxosebacic acid complex
Structure: 5-aminolaevulinic acid dehydratase. Chain: a. Synonym: alad, porphobilinogen synthase. Engineered: yes. Other_details: complex with 4,7-dioxosebacic acid
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Strain: ns1(jm109/pns1). Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Octamer (from PDB file)
1.75Å     R-factor:   0.239     R-free:   0.308
Authors: P.T.Erskine,L.Coates,R.Newbold,A.A.Brindley,F.Stauffer, S.P.Wood,M.J.Warren,J.B.Cooper,P.M.Shoolingin-Jordan, R.Neier
Key ref:
P.T.Erskine et al. (2001). The X-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with two diacid inhibitors. FEBS Lett, 503, 196-200. PubMed id: 11513881 DOI: 10.1016/S0014-5793(01)02721-1
18-Jul-01     Release date:   02-Aug-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P05373  (HEM2_YEAST) -  Delta-aminolevulinic acid dehydratase
342 a.a.
340 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 = DSB)
matches with 43.00% 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     6 terms  


    Added reference    
DOI no: 10.1016/S0014-5793(01)02721-1 FEBS Lett 503:196-200 (2001)
PubMed id: 11513881  
The X-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with two diacid inhibitors.
P.T.Erskine, L.Coates, R.Newbold, A.A.Brindley, F.Stauffer, S.P.Wood, M.J.Warren, J.B.Cooper, P.M.Shoolingin-Jordan, R.Neier.
The structures of 5-aminolaevulinic acid dehydratase complexed with two irreversible inhibitors (4-oxosebacic acid and 4,7-dioxosebacic acid) have been solved at high resolution. Both inhibitors bind by forming a Schiff base link with Lys 263 at the active site. Previous inhibitor binding studies have defined the interactions made by only one of the two substrate moieties (P-side substrate) which bind to the enzyme during catalysis. The structures reported here provide an improved definition of the interactions made by both of the substrate molecules (A- and P-side substrates). The most intriguing result is the novel finding that 4,7-dioxosebacic acid forms a second Schiff base with the enzyme involving Lys 210. It has been known for many years that P-side substrate forms a Schiff base (with Lys 263) but until now there has been no evidence that binding of A-side substrate involves formation of a Schiff base with the enzyme. A catalytic mechanism involving substrate linked to the enzyme through Schiff bases at both the A- and P-sites is proposed.
  Selected figure(s)  
Figure 1.
Fig. 1. The reaction catalysed by 5-aminolaevulinic acid dehydratase (ALAD). Two molecules of 5-aminolaevulinic acid are condensed to form the pyrrole porphobilinogen.
Figure 3.
Fig. 3. The refined electron density maps (shown in purple) for the inhibitors 4,7-dioxosebacic acid at 1.75 Å resolution (top) and 4-oxosebacic acid at 1.8 Å resolution (bottom). The maps are contoured at 1.5 rms (top) and 1.2 rms (bottom).
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS Lett (2001, 503, 196-200) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20354739 N.Sawada, N.Nagahara, F.Arisaka, K.Mitsuoka, and M.Minami (2011).
Redox and metal-regulated oligomeric state for human porphobilinogen synthase activation.
  Amino Acids, 41, 173-180.  
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.  
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.  
16304458 L.Coates, G.Beaven, P.T.Erskine, S.I.Beale, S.P.Wood, P.M.Shoolingin-Jordan, and J.B.Cooper (2005).
Structure of Chlorobium vibrioforme 5-aminolaevulinic acid dehydratase complexed with a diacid inhibitor.
  Acta Crystallogr D Biol Crystallogr, 61, 1594-1598.
PDB code: 2c1h
15747133 N.Sawada, N.Nagahara, T.Sakai, Y.Nakajima, M.Minami, and T.Kawada (2005).
The activation mechanism of human porphobilinogen synthase by 2-mercaptoethanol: intrasubunit transfer of a reserve zinc ion and coordination with three cysteines in the active center.
  J Biol Inorg Chem, 10, 199-207.  
16131755 P.T.Erskine, L.Coates, R.Newbold, A.A.Brindley, F.Stauffer, G.D.Beaven, R.Gill, A.Coker, S.P.Wood, M.J.Warren, P.M.Shoolingin-Jordan, R.Neier, and J.B.Cooper (2005).
Structure of yeast 5-aminolaevulinic acid dehydratase complexed with the inhibitor 5-hydroxylaevulinic acid.
  Acta Crystallogr D Biol Crystallogr, 61, 1222-1226.
PDB code: 1w31
12897770 S.Breinig, J.Kervinen, L.Stith, A.S.Wasson, R.Fairman, A.Wlodawer, A.Zdanov, and E.K.Jaffe (2003).
Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase.
  Nat Struct Biol, 10, 757-763.
PDB code: 1pv8
11909869 E.K.Jaffe, J.Kervinen, J.Martins, F.Stauffer, R.Neier, A.Wlodawer, and A.Zdanov (2002).
Species-specific inhibition of porphobilinogen synthase by 4-oxosebacic acid.
  J Biol Chem, 277, 19792-19799.
PDB codes: 1l6s 1l6y
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.