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Lyase PDB id
1j93
Jmol
Contents
Protein chain
343 a.a. *
Ligands
SO4 ×5
Waters ×231
* Residue conservation analysis
PDB id:
1j93
Name: Lyase
Title: Crystal structure and substrate binding modeling of the uroporphyrinogen-iii decarboxylase from nicotiana tabacum: implications for the catalytic mechanism
Structure: Uroporphyrinogen decarboxylase. Chain: a. Synonym: urod. Engineered: yes
Source: Nicotiana tabacum. Common tobacco. Organism_taxid: 4097. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
Resolution:
2.30Å     R-factor:   0.209     R-free:   0.256
Authors: B.M.Martins,B.Grimm,H.-P.Mock,R.Huber,A.Messerschmidt
Key ref:
B.M.Martins et al. (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. PubMed id: 11524417 DOI: 10.1074/jbc.M104759200
Date:
23-May-01     Release date:   17-Oct-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q42967  (DCUP_TOBAC) -  Uroporphyrinogen decarboxylase, chloroplastic
Seq:
Struc: 		391 a.a.
343 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.1.1.37  - Uroporphyrinogen decarboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Porphyrin Biosynthesis (later stages)
      Reaction: Uroporphyrinogen III = coproporphyrinogen + 4 CO2
Uroporphyrinogen III
 = coproporphyrinogen
 + 4 × CO(2)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     plastid   2 terms 
  Biological process     porphyrin biosynthetic process   2 terms 
  Biochemical function     lyase activity     3 terms  

 

 
    Added reference    
 
 
DOI no: 10.1074/jbc.M104759200 J Biol Chem 276:44108-44116 (2001)
PubMed id: 11524417  
 
 
Crystal structure and substrate binding modeling of the uroporphyrinogen-III decarboxylase from Nicotiana tabacum. Implications for the catalytic mechanism.
B.M.Martins, B.Grimm, H.P.Mock, R.Huber, A.Messerschmidt.
 
  ABSTRACT  
 
The enzymatic catalysis of many biological processes of life is supported by the presence of cofactors and prosthetic groups originating from the common tetrapyrrole precursor uroporphyrinogen-III. Uroporphyrinogen-III decarboxylase catalyzes its conversion into coproporphyrinogen-III, leading in plants to chlorophyll and heme biosynthesis. Here we report the first crystal structure of a plant (Nicotiana tabacum) uroporphyrinogen-III decarboxylase, together with the molecular modeling of substrate binding in tobacco and human enzymes. Its structural comparison with the homologous human protein reveals a similar catalytic cleft with six invariant polar residues, Arg(32), Arg(36), Asp(82), Ser(214) (Thr in Escherichia coli), Tyr(159), and His(329) (tobacco numbering). The functional relationships obtained from the structural and modeling analyses of both enzymes allowed the proposal for a refined catalytic mechanism. Asp(82) and Tyr(159) seem to be the catalytic functional groups, whereas the other residues may serve in substrate recognition and binding, with Arg(32) steering its insertion. The crystallographic dimer appears to represent the protein dimer under physiological conditions. The dimeric arrangement offers a plausible mechanism at least for the first two (out of four) decarboxylation steps.
 
  Selected figure(s)  
 
Figure 4.
Fig. 4. Stereo representation of the modeling calculations for the enzyme substrate complex of human UROD. A, the initial substrate enzyme complex. B, the complex after the energy minimization. The dashed lines represent the putative electrostatic interactions between the substrate and the enzyme. Labeled residues are numbered according to the human amino acid sequence (16). For simplicity only rings A and D from the substrate are labeled. Image was produced with Bobscript (43) and Raster3D (44). 		Figure 6.
Fig. 6. Putative reaction sequence for the uroporphyrinogen-III decarboxylase catalysis. For simplicity only one pyrrole ring moiety is depicted. Scheme was produced with ISISTM/DRAW.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 44108-44116) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20941734 E.A.Bushnell, E.Erdtman, J.Llano, L.A.Eriksson, and J.W.Gauld (2011).
The first branching point in porphyrin biosynthesis: A systematic docking, molecular dynamics and quantum mechanical/molecular mechanical study of substrate binding and mechanism of uroporphyrinogen-III decarboxylase.
  J Comput Chem, 32, 822-834.  
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.  
19419417 C.Badenas, J.To-Figueras, J.D.Phillips, C.A.Warby, C.Muñoz, and C.Herrero (2009).
Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives.
  Clin Genet, 75, 346-353.  
19362562 J.D.Phillips, C.A.Warby, F.G.Whitby, J.P.Kushner, and C.P.Hill (2009).
Substrate shuttling between active sites of uroporphyrinogen decarboxylase is not required to generate coproporphyrinogen.
  J Mol Biol, 389, 306-314.
PDB codes: 3gvq 3gvr 3gvv 3gvw
18988736 C.A.Lewis, and R.Wolfenden (2008).
Uroporphyrinogen decarboxylation as a benchmark for the catalytic proficiency of enzymes.
  Proc Natl Acad Sci U S A, 105, 17328-17333.  
18460784 M.Saito, S.Watanabe, H.Yoshikawa, and H.Nakamoto (2008).
Interaction of the molecular chaperone HtpG with uroporphyrinogen decarboxylase in the cyanobacterium Synechococcus elongatus PCC 7942.
  Biosci Biotechnol Biochem, 72, 1394-1397.  
18846277 T.Masuda, and Y.Fujita (2008).
Regulation and evolution of chlorophyll metabolism.
  Photochem Photobiol Sci, 7, 1131-1149.  
17496980 A.B.Juárez, C.Aldonatti, M.S.Vigna, and M.d.e.l. .C.Ríos de Molina (2007).
Studies on uroporphyrinogen decarboxylase from Chlorella kessleri (Trebouxiophyceae, Chlorophyta).
  Can J Microbiol, 53, 303-312.  
17122346 J.Fan, Q.Liu, Q.Hao, M.Teng, and L.Niu (2007).
Crystal structure of uroporphyrinogen decarboxylase from Bacillus subtilis.
  J Bacteriol, 189, 3573-3580.
PDB code: 2inf
14633982 J.D.Phillips, F.G.Whitby, J.P.Kushner, and C.P.Hill (2003).
Structural basis for tetrapyrrole coordination by uroporphyrinogen decarboxylase.
  EMBO J, 22, 6225-6233.
PDB codes: 1r3q 1r3r 1r3s 1r3t 1r3v 1r3w 1r3y
  12429089 J.P.Keller, P.M.Smith, J.Benach, D.Christendat, G.T.deTitta, and J.F.Hunt (2002).
The crystal structure of MT0146/CbiT suggests that the putative precorrin-8w decarboxylase is a methyltransferase.
  Structure, 10, 1475-1487.
PDB codes: 1f38 1kxz 1l3b 1l3c 1l3i
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 codes are shown on the right.