PDBsum entry 1qmk

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protein metals links
Dehydratase PDB id
Protein chain
328 a.a.
_PB ×2
Waters ×370
Superseded by: 1qnv
PDB id:
Name: Dehydratase
Title: Yeast 5-aminolaevulinic acid dehydratase lead (pb) complex
Structure: 5-aminolaevulinic acid dehydratase. Chain: a. Synonym: aladh, porphobilinogen synthase. Other_details: pb acetate co-crystal
Source: Saccharomyces cerevisiae. Baker's yeast. Strain: ns1(jm109/pns1). Plasmid: pns1. Gene: hem2
Biol. unit: Homo-Octamer (from PDB file)
2.50Å     R-factor:   0.290     R-free:   0.410
Authors: P.T.Erskine,N.Senior,M.J.Warren,S.P.Wood,J.B.Cooper
Key ref:
P.T.Erskine et al. (2000). MAD analyses of yeast 5-aminolaevulinate dehydratase: their use in structure determination and in defining the metal-binding sites. Acta Crystallogr D Biol Crystallogr, 56, 421-430. PubMed id: 10739915 DOI: 10.1107/S0907444900000597
01-Oct-99     Release date:   06-Oct-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P05373  (HEM2_YEAST) -  Delta-aminolevulinic acid dehydratase
342 a.a.
328 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
= porphobilinogen
+ 2 × H(2)O
      Cofactor: Zinc
Molecule diagrams generated from .mol files obtained from the KEGG ftp site


    Added reference    
DOI no: 10.1107/S0907444900000597 Acta Crystallogr D Biol Crystallogr 56:421-430 (2000)
PubMed id: 10739915  
MAD analyses of yeast 5-aminolaevulinate dehydratase: their use in structure determination and in defining the metal-binding sites.
P.T.Erskine, E.M.Duke, I.J.Tickle, N.M.Senior, M.J.Warren, J.B.Cooper.
MAD experiments attempting to solve the structure of 5--aminolaevulinic acid dehydratase using Zn and Pb edges are described. The data obtained proved insufficient for a complete structure solution but were invaluable in subsequent identification of metal-binding sites using anomalous difference Fourier analyses once the structure of the enzyme had been solved. These sites include the highly inhibitory substitution of an enzymic cofactor Zn(2+) ion by Pb(2+) ions, which represents a major contribution towards understanding the molecular basis of lead poisoning. The MAD data collected at the Pb edge were also used with isomorphous replacement data from the same Pb co-crystal and a Hg co-crystal to provide the first delineation of the enzyme's quaternary structure. In this MADIR analysis, the Hg co-crystal data were treated as native data. Anomalous difference Fouriers were again used, revealing that Hg(2+) had substituted for the same Zn(2+) cofactor ion as had Pb(2+), a finding of fundamental importance for the understanding of mercury poisoning. In addition, Pt(2+) ions were found to bind at the same place in the structure. The refined structures of the Pb- and the Hg-complexed enzymes are presented at 2.5 and 3.0 A resolution, respectively.
  Selected figure(s)  
Figure 4.
Figure 4 S. cerevisiae ALAD Pb edge (PX 9.5 MAD [1] data) anomalous difference Patterson at 3.0 resolution, u = Harker section. The site marked by a cross was tried in a superposition function in VECSUM but failed to bring back other sites. It produced poor phasing statistics in MLPHARE. From the isomorphous replacement processing of the PX 9.6 data from this crystal against the isomorphous Hg co-crystal the site corresponds to one of the Pb sites. The major axial peak at the right corresponds to peaks in that processing found to have arisen from cross vectors between the two lead sites. The map is contoured at 94% r.m.s.
Figure 6.
Figure 6 A MADIR approach with data from the S. cerevisiae ALAD lead acetate co-crystal allowed the calculation of an electron-density map at 3.0 resolution in which there was a clear solvent boundary. The map was extended to show the overall organization of the octamer. Here, four subunits of the ALAD octamer can be seen disposed around the crystallographic fourfold axis.
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2000, 56, 421-430) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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.  
17609383 D.S.Touw, C.E.Nordman, J.A.Stuckey, and V.L.Pecoraro (2007).
Identifying important structural characteristics of arsenic resistance proteins by using designed three-stranded coiled coils.
  Proc Natl Acad Sci U S A, 104, 11969-11974.
PDB code: 2jgo
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.  
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.  
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
10992288 K.Kim, and D.M.Ogrydziak (2000).
Current awareness on yeast.
  Yeast, 16, 1253-1260.  
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.