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PDBsum entry 1aw5

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protein metals links
Dehydratase PDB id
1aw5
Jmol
Contents
Protein chain
326 a.a. *
Metals
_ZN ×2
Waters ×307
* Residue conservation analysis
PDB id:
1aw5
Name: Dehydratase
Title: 5-aminolevulinate dehydratase from saccharomyces cerevisiae
Structure: 5-aminolevulinate dehydratase. Chain: a. Synonym: porphobilinogen synthase. Engineered: yes. Mutation: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Cell_line: b834. Cellular_location: cytosol. Gene: hem2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Octamer (from PDB file)
Resolution:
2.30Å     R-factor:   0.198     R-free:   0.270
Authors: P.T.Erskine,J.B.Cooper,S.P.Wood
Key ref: P.T.Erskine et al. (1997). X-ray structure of 5-aminolaevulinate dehydratase, a hybrid aldolase. Nat Struct Biol, 4, 1025-1031. PubMed id: 9406553
Date:
09-Oct-97     Release date:   21-Oct-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P05373  (HEM2_YEAST) -  Delta-aminolevulinic acid dehydratase
Seq:
Struc:
342 a.a.
326 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.4.2.1.24  - Porphobilinogen synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
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     6 terms  

 

 
    Added reference    
 
 
Nat Struct Biol 4:1025-1031 (1997)
PubMed id: 9406553  
 
 
X-ray structure of 5-aminolaevulinate dehydratase, a hybrid aldolase.
P.T.Erskine, N.Senior, S.Awan, R.Lambert, G.Lewis, I.J.Tickle, M.Sarwar, P.Spencer, P.Thomas, M.J.Warren, P.M.Shoolingin-Jordan, S.P.Wood, J.B.Cooper.
 
  ABSTRACT  
 
5-Aminolaevulinate dehydratase (ALAD) is a homo-octameric metallo-enzyme that catalyses the formation of porphobilinogen from 5-aminolaevulinic acid. The structure of the yeast enzyme has been solved to 2.3 A resolution, revealing that each subunit adopts a TIM barrel fold with a 39 residue N-terminal arm. Pairs of monomers wrap their arms around each other to form compact dimers and these associate to form a 422 symmetric octamer. All eight active sites are on the surface of the octamer and possess two lysine residues (210 and 263), one of which, Lys 263, forms a Schiff base link to the substrate. The two lysine side chains are close to two zinc binding sites one of which is formed by three cysteine residues (133, 135 and 143) while the other involves Cys 234 and His 142. ALAD has features at its active site that are common to both metallo- and Schiff base-aldolases and therefore represents an intriguing combination of both classes of enzyme. Lead ions, which inhibit ALAD potently, replace the zinc bound to the enzyme's unique triple-cysteine site.
 

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.  
21253649 S.M.Quintal, Q.A.dePaula, and N.P.Farrell (2011).
Zinc finger proteins as templates for metal ion exchange and ligand reactivity. Chemical and biological consequences.
  Metallomics, 3, 121-139.  
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
  20859984 K.P.Neupane, and V.L.Pecoraro (2010).
Probing a homoleptic PbS3 coordination environment in a designed peptide using 207Pb NMR spectroscopy: implications for understanding the molecular basis of lead toxicity.
  Angew Chem Int Ed Engl, 49, 8177-8180.  
  20865533 U.D.Ramirez, F.Myachina, L.Stith, and E.K.Jaffe (2010).
Docking to large allosteric binding sites on protein surfaces.
  Adv Exp Med Biol, 680, 481-488.  
19229934 O.Iranzo, T.Jakusch, K.H.Lee, L.Hemmingsen, and V.L.Pecoraro (2009).
The correlation of 113Cd NMR and 111mCd PAC spectroscopies provides a powerful approach for the characterization of the structure of Cd(II)-substituted Zn(II) proteins.
  Chemistry, 15, 3761-3772.  
18795796 B.Kokona, D.J.Rigotti, A.S.Wasson, S.H.Lawrence, E.K.Jaffe, and R.Fairman (2008).
Probing the oligomeric assemblies of pea porphobilinogen synthase by analytical ultracentrifugation.
  Biochemistry, 47, 10649-10656.  
18684507 M.Kirberger, and J.J.Yang (2008).
Structural differences between Pb2+- and Ca2+-binding sites in proteins: implications with respect to toxicity.
  J Inorg Biochem, 102, 1901-1909.  
19015748 R.Inoue, and R.Akagi (2008).
Co-synthesis of Human delta-Aminolevulinate Dehydratase (ALAD) Mutants with the Wild-type Enzyme in Cell-free System-Critical Importance of Conformation on Enzyme Activity-.
  J Clin Biochem Nutr, 43, 143-153.  
19484137 G.Parkin (2007).
Applications of Tripodal [S(3)] and [Se(3)] L(2)X Donor Ligands to Zinc, Cadmium and Mercury Chemistry: Organometallic and Bioinorganic Perspectives.
  New J Chem, 31, 1996-2014.  
16596690 K.H.Lee, C.Cabello, L.Hemmingsen, E.N.Marsh, and V.L.Pecoraro (2006).
Using nonnatural amino acids to control metal-coordination number in three-stranded coiled coils.
  Angew Chem Int Ed Engl, 45, 2864-2868.  
16855818 M.Matzapetakis, D.Ghosh, T.C.Weng, J.E.Penner-Hahn, and V.L.Pecoraro (2006).
Peptidic models for the binding of Pb(II), Bi(III) and Cd(II) to mononuclear thiolate binding sites.
  J Biol Inorg Chem, 11, 876-890.  
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
15555082 D.W.Bollivar, C.Clauson, R.Lighthall, S.Forbes, B.Kokona, R.Fairman, L.Kundrat, and E.K.Jaffe (2004).
Rhodobacter capsulatus porphobilinogen synthase, a high activity metal ion independent hexamer.
  BMC Biochem, 5, 17.  
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
11828463 F.Stauffer, E.Zizzari, C.Engeloch-Jarret, J.P.Faurite, J.Bobálová, and R.Neier (2001).
Inhibition studies of porphobilinogen synthase from Escherichia coli differentiating between the two recognition sites.
  Chembiochem, 2, 343-354.  
11282351 H.A.Godwin (2001).
The biological chemistry of lead.
  Curr Opin Chem Biol, 5, 223-227.  
11345546 M.C.Zaccaro, C.Salazar, G.Zulpa de Caire, M.Storni de Cano, and A.M.Stella (2001).
Lead toxicity in cyanobacterial porphyrin metabolism.
  Environ Toxicol, 16, 61-67.  
10712932 C.Jarret, F.Stauffer, M.E.Henz, M.Marty, R.M.Lüönd, J.Bobálová, P.Schürmann, and R.Neier (2000).
Inhibition of Escherichia coli porphobilinogen synthase using analogs of postulated intermediates.
  Chem Biol, 7, 185-196.  
10644722 E.K.Jaffe, M.Volin, C.R.Bronson-Mullins, R.L.Dunbrack, J.Kervinen, J.Martins, J.F.Quinlan, M.H.Sazinsky, E.M.Steinhouse, and A.T.Yeung (2000).
An artificial gene for human porphobilinogen synthase allows comparison of an allelic variation implicated in susceptibility to lead poisoning.
  J Biol Chem, 275, 2619-2626.  
10913315 J.Kervinen, R.L.Dunbrack, S.Litwin, J.Martins, R.C.Scarrow, M.Volin, A.T.Yeung, E.Yoon, and E.K.Jaffe (2000).
Porphobilinogen synthase from pea: expression from an artificial gene, kinetic characterization, and novel implications for subunit interactions.
  Biochemistry, 39, 9018-9029.  
  10386874 P.T.Erskine, R.Newbold, J.Roper, A.Coker, M.J.Warren, P.M.Shoolingin-Jordan, S.P.Wood, and J.B.Cooper (1999).
The Schiff base complex of yeast 5-aminolaevulinic acid dehydratase with laevulinic acid.
  Protein Sci, 8, 1250-1256.
PDB code: 1ylv
10336376 R.Schleif (1999).
Arm-domain interactions in proteins: a review.
  Proteins, 34, 1-3.  
9644976 M.J.Warren, J.B.Cooper, S.P.Wood, and P.M.Shoolingin-Jordan (1998).
Lead poisoning, haem synthesis and 5-aminolaevulinic acid dehydratase.
  Trends Biochem Sci, 23, 217-221.  
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.