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PDBsum entry 1b4e
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protein ligands metals links
Lyase PDB id
1b4e

 

 

 

 

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Contents
Protein chain
323 a.a. *
Ligands
SO4 ×3
SHF
GOL ×3
Metals
_ZN ×3
Waters ×371
* Residue conservation analysis
PDB id:
1b4e
Name: Lyase
Title: X-ray structure of 5-aminolevulinic acid dehydratase complexed with the inhibitor levulinic acid
Structure: Protein (5-aminolevulinic acid dehydratase). Chain: a. Synonym: alad. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: hem2. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Octamer (from PDB file)
Resolution:
2.00Å     R-factor:   0.188     R-free:   0.255
Authors: P.T.Erskine,J.B.Cooper,G.Lewis,P.Spencer,S.P.Wood,P.M.Shoolingin- Jordan
Key ref:
P.T.Erskine et al. (1999). X-ray structure of 5-aminolevulinic acid dehydratase from Escherichia coli complexed with the inhibitor levulinic acid at 2.0 A resolution. Biochemistry, 38, 4266-4276. PubMed id: 10194344 DOI: 10.1021/bi982137w
Date:
19-Dec-98     Release date:   17-Dec-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
P0ACB2  (HEM2_ECOLI) -  Delta-aminolevulinic acid dehydratase from Escherichia coli (strain K12)
Seq:
Struc: 		324 a.a.
323 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 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 + H+
2 × 5-aminolevulinate
Bound ligand (Het Group name = SHF)
matches with 77.78% similarity 		= porphobilinogen
 + 2 × H2O
 + H(+)
      Cofactor: Zn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1021/bi982137w Biochemistry 38:4266-4276 (1999)
PubMed id: 10194344  
 
 
X-ray structure of 5-aminolevulinic acid dehydratase from Escherichia coli complexed with the inhibitor levulinic acid at 2.0 A resolution.
P.T.Erskine, E.Norton, J.B.Cooper, R.Lambert, A.Coker, G.Lewis, P.Spencer, M.Sarwar, S.P.Wood, M.J.Warren, P.M.Shoolingin-Jordan.
 
  ABSTRACT  
 
5-Aminolevulinic acid dehydratase (ALAD), an early enzyme of the tetrapyrrole biosynthesis pathway, catalyzes the dimerization of 5-aminolevulinic acid to form the pyrrole, porphobilinogen. ALAD from Escherichia coli is shown to form a homo-octameric structure with 422 symmetry in which each subunit adopts the TIM barrel fold with a 30-residue N-terminal arm. Pairs of monomers associate with their arms wrapped around each other. Four of these dimers interact, principally via their arm regions, to form octamers in which each active site is located on the surface. The active site contains two lysine residues (195 and 247), one of which (Lys 247) forms a Schiff base link with the bound substrate analogue, levulinic acid. Of the two substrate binding sites (referred to as A and P), our analysis defines the residues forming the P-site, which is where the first ALA molecule to associate with the enzyme binds. The carboxyl group of the levulinic acid moiety forms hydrogen bonds with the side chains of Ser 273 and Tyr 312. In proximity to the levulinic acid is a zinc binding site formed by three cysteines (Cys 120, 122, and 130) and a solvent molecule. We infer that the second substrate binding site (or A-site) is located between the triple-cysteine zinc site and the bound levulinic acid moiety. Two invariant arginine residues in a loop covering the active site (Arg 205 and Arg 216) appear to be appropriately placed to bind the carboxylate of the A-site substrate. Another metal binding site, close to the active site flap, in which a putative zinc ion is coordinated by a carboxyl and five solvent molecules may account for the activating properties of magnesium ions.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20865477 A.Pietrangelo (2010).
The porphyrias: pathophysiology.
  Intern Emerg Med, 5, S65-S71.  
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.  
20029108 G.Wellenreuther, V.Parthasarathy, and W.Meyer-Klaucke (2010).
Towards a black-box for biological EXAFS data analysis. II. Automatic BioXAS Refinement and Analysis (ABRA).
  J Synchrotron Radiat, 17, 25-35.  
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
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.  
19267692 S.A.Lobo, A.Brindley, M.J.Warren, and L.M.Saraiva (2009).
Functional characterization of the early steps of tetrapyrrole biosynthesis and modification in Desulfovibrio vulgaris Hildenborough.
  Biochem J, 420, 317-325.  
19764719 S.Severance, and I.Hamza (2009).
Trafficking of heme and porphyrins in metazoa.
  Chem Rev, 109, 4596-4616.  
18391407 B.Lohkamp, and D.Dobritzsch (2008).
A mixture of fortunes: the curious determination of the structure of Escherichia coli BL21 Gab protein.
  Acta Crystallogr D Biol Crystallogr, 64, 407-415.
PDB code: 2r6s
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.  
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
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
14638682 S.Dhanasekaran, N.R.Chandra, B.K.Chandrasekhar Sagar, P.N.Rangarajan, and G.Padmanaban (2004).
Delta-aminolevulinic acid dehydratase from Plasmodium falciparum: indigenous versus imported.
  J Biol Chem, 279, 6934-6942.  
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
11985624 A.Katayama, A.Tsujii, A.Wada, T.Nishino, and A.Ishihama (2002).
Systematic search for zinc-binding proteins in Escherichia coli.
  Eur J Biochem, 269, 2403-2413.  
12010463 D.V.Vavilin, and W.F.Vermaas (2002).
Regulation of the tetrapyrrole biosynthetic pathway leading to heme and chlorophyll in plants and cyanobacteria.
  Physiol Plant, 115, 9.  
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
11524417 B.M.Martins, B.Grimm, H.P.Mock, R.Huber, and A.Messerschmidt (2001).
Crystal structure and substrate binding modeling of the uroporphyrinogen-III decarboxylase from Nicotiana tabacum. Implications for the catalytic mechanism.
  J Biol Chem, 276, 44108-44116.
PDB code: 1j93
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.  
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.  
10666591 E.K.Jaffe (2000).
The porphobilinogen synthase family of metalloenzymes.
  Acta Crystallogr D Biol Crystallogr, 56, 115-128.  
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.  
10739915 P.T.Erskine, E.M.Duke, I.J.Tickle, N.M.Senior, M.J.Warren, and J.B.Cooper (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.
PDB codes: 1qmk 1qml 1qnv
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.

 

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