PDBsum entry 1h7n

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protein ligands metals links
Dehydratase PDB id
Protein chain
340 a.a. *
Waters ×382
* Residue conservation analysis
PDB id:
Name: Dehydratase
Title: Schiff-base complex of yeast 5-aminolaevulinic acid dehydratase with laevulinic acid at 1.6 a resolution
Structure: 5-aminolaevulinic acid dehydratase. Chain: a. Synonym: alad, porphobilinogen synthase. Engineered: yes. Other_details: schiff-base link between laevulinic acid inhibitor (het group a1341) and lysine 263
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Octamer (from PDB file)
1.6Å     R-factor:   0.217     R-free:   0.265
Authors: P.T.Erskine,R.Newbold,A.A.Brindley,S.P.Wood, P.M.Shoolingin-Jordan,M.J.Warren,J.B.Cooper
Key ref:
P.T.Erskine et al. (2001). The x-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with substrate and three inhibitors. J Mol Biol, 312, 133-141. PubMed id: 11545591 DOI: 10.1006/jmbi.2001.4947
09-Jul-01     Release date:   10-Jul-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 = SHF)
matches with 77.00% 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: 10.1006/jmbi.2001.4947 J Mol Biol 312:133-141 (2001)
PubMed id: 11545591  
The x-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with substrate and three inhibitors.
P.T.Erskine, R.Newbold, A.A.Brindley, S.P.Wood, P.M.Shoolingin-Jordan, M.J.Warren, J.B.Cooper.
The structures of 5-aminolaevulinic acid dehydratase (ALAD) complexed with substrate (5-aminolaevulinic acid) and three inhibitors: laevulinic acid, succinylacetone and 4-keto-5-aminolaevulinic acid, have been solved at high resolution. The ligands all bind by forming a covalent link with Lys263 at the active site. The structures define the interactions made by one of the two substrate moieties that bind to the enzyme during catalysis. All of the inhibitors induce a significant ordering of the flap covering the active site. Succinylacetone appears to be unique by inducing a number of conformational changes in loops covering the active site, which may be important for understanding the co-operative properties of ALAD enzymes. Succinylacetone is produced in large amounts by patients suffering from the hereditary disease type I tyrosinaemia and its potent inhibition of ALAD also has implications for the pathology of this disease. The most intriguing result is that obtained with 4-keto-5-amino-hexanoic acid, which seems to form a stable carbinolamine intermediate with Lys263. It appears that we have defined the structure of an intermediate of Schiff base formation that the substrate forms upon binding to the P-site of the enzyme.
  Selected figure(s)  
Figure 4.
Figure 4. The electron density for each of the ALAD ligands bound to Lys263: (a) substrate ALA at 1.7 Å res- olution; (b) laevulinic acid (LA) at 1.6 Å resolution; (c) succinylacetone (SA) at 2.0 Å resolution; and (d) 4-keto- 5-amino-hexanoic acid (KAH) at 1.64 Å resolution. All maps are contoured at 1.0 rms. The Lys263 side-chain can be seen behind the inhibitor moiety. The two confor- mers adopted by ALA and LA are coloured slightly different shades of green in (a) and (b).
Figure 6.
Figure 6. The electron density for 4-keto-5-amino-hexanoic acid (KAH) contoured at 1.2 rms show- ing the residues it interacts with. The inhibitor has been modelled as a carbinolamine intermediate (labelled KAT).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 312, 133-141) copyright 2001.  
  Figures were selected by an automated process.  

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.  
19530727 H.Huang, H.Y.Kim, I.D.Kozekov, Y.J.Cho, H.Wang, A.Kozekova, T.M.Harris, C.J.Rizzo, and M.P.Stone (2009).
Stereospecific formation of the (R)-gamma-hydroxytrimethylene interstrand N2-dG:N2-dG cross-link arising from the gamma-OH-1,N2-propano-2'-deoxyguanosine adduct in the 5'-CpG-3' DNA sequence.
  J Am Chem Soc, 131, 8416-8424.  
20302542 R.Rilk-van Gessel, and H.Kayser (2007).
Porphobilinogen synthase from the butterfly, Pieris brassicae: purification and comparative characterization.
  J Insect Sci, 7, 1.  
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
15710608 L.Tang, L.Stith, and E.K.Jaffe (2005).
Substrate-induced interconversion of protein quaternary structure isoforms.
  J Biol Chem, 280, 15786-15793.  
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
12573695 E.K.Jaffe (2003).
An unusual phylogenetic variation in the metal ion binding sites of porphobilinogen synthase.
  Chem Biol, 10, 25-34.  
12794073 L.Kundrat, J.Martins, L.Stith, R.L.Dunbrack, and E.K.Jaffe (2003).
A structural basis for half-of-the-sites metal binding revealed in Drosophila melanogaster porphobilinogen synthase.
  J Biol Chem, 278, 31325-31330.  
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.