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PDBsum entry 1uro

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Lyase PDB id
1uro
Jmol
Contents
Protein chain
357 a.a. *
Ligands
BME
Waters ×282
* Residue conservation analysis
PDB id:
1uro
Name: Lyase
Title: Uroporphyrinogen decarboxylase
Structure: Protein (uroporphyrinogen decarboxylase). Chain: a. Synonym: uro-d, urod. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Other_details: his-tag cleaved
Biol. unit: Dimer (from PDB file)
Resolution:
1.80Å     R-factor:   0.184     R-free:   0.233
Authors: F.G.Whitby,J.D.Phillips,J.P.Kushner,C.P.Hill
Key ref:
F.G.Whitby et al. (1998). Crystal structure of human uroporphyrinogen decarboxylase. EMBO J, 17, 2463-2471. PubMed id: 9564029 DOI: 10.1093/emboj/17.9.2463
Date:
21-Aug-98     Release date:   26-Aug-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P06132  (DCUP_HUMAN) -  Uroporphyrinogen decarboxylase
Seq:
Struc:
367 a.a.
357 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)
Bound ligand (Het Group name = BME)
matches with 40.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   3 terms 
  Biological process     small molecule metabolic process   6 terms 
  Biochemical function     lyase activity     3 terms  

 

 
    Added reference    
 
 
DOI no: 10.1093/emboj/17.9.2463 EMBO J 17:2463-2471 (1998)
PubMed id: 9564029  
 
 
Crystal structure of human uroporphyrinogen decarboxylase.
F.G.Whitby, J.D.Phillips, J.P.Kushner, C.P.Hill.
 
  ABSTRACT  
 
Uroporphyrinogen decarboxylase (URO-D) catalyzes the fifth step in the heme biosynthetic pathway, converting uroporphyrinogen to coproporphyrinogen by decarboxylating the four acetate side chains of the substrate. This activity is essential in all organisms, and subnormal activity of URO-D leads to the most common form of porphyria in humans, porphyria cutanea tarda (PCT). We have determined the crystal structure of recombinant human URO-D at 1.60 A resolution. The 40.8 kDa protein is comprised of a single domain containing a (beta/alpha)8-barrel with a deep active site cleft formed by loops at the C-terminal ends of the barrel strands. Many conserved residues cluster at this cleft, including the invariant side chains of Arg37, Arg41 and His339, which probably function in substrate binding, and Asp86, Tyr164 and Ser219, which may function in either binding or catalysis. URO-D is a dimer in solution (Kd = 0.1 microM), and this dimer also appears to be formed in the crystal. Assembly of the dimer juxtaposes the active site clefts of the monomers, suggesting a functionally important interaction between the catalytic centers.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Enzymatic conversion of uroporphyrinogen III to coproporphyrinogen III. A = acetate, P = propionate, M = methyl. The acetate side chains of uroporphyrinogen III are decarboxylated to methyl groups with the liberation of four molecules of carbon dioxide. In the type-I isomer, the acetate and propionate side chains of the D ring are ordered as on the other pyrrole rings, and the molecule is symmetrical.
Figure 6.
Figure 6 Schematic representation of the strands in the -barrel. -Strands are shown as broad arrows and numbered from the most N-terminal (S1) to the most C-terminal (S8). Residues that point toward the barrel core are shown as white circles, and those that point out of the barrel are shown as black circles. Hydrogen bonds are represented by thin lines. The distortion in the barrel structure between strands S1 and S2 is compensated by the hydrogen bond network involving Gln38 and Asp79.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1998, 17, 2463-2471) copyright 1998.  
  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.  
21270338 E.Ito, S.Yue, E.H.Moriyama, A.B.Hui, I.Kim, W.Shi, N.M.Alajez, N.Bhogal, G.Li, A.Datti, A.D.Schimmer, B.C.Wilson, P.P.Liu, D.Durocher, B.G.Neel, B.O'Sullivan, B.Cummings, R.Bristow, J.Wrana, and F.F.Liu (2011).
Uroporphyrinogen decarboxylase is a radiosensitizing target for head and neck cancer.
  Sci Transl Med, 3, 67ra7.  
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.  
  19656450 C.A.Warby, J.D.Phillips, H.A.Bergonia, F.G.Whitby, C.P.Hill, and J.P.Kushner (2009).
Structural and kinetic characterization of mutant human uroporphyrinogen decarboxylases.
  Cell Mol Biol (Noisy-le-grand), 55, 40-45.
PDB codes: 3gw0 3gw3
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.  
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
17627795 M.Méndez, P.Poblete-Gutiérrez, M.García-Bravo, T.Wiederholt, M.J.Morán-Jiménez, H.F.Merk, M.C.Garrido-Astray, J.Frank, A.Fontanellas, and R.Enríquez de Salamanca (2007).
Molecular heterogeneity of familial porphyria cutanea tarda in Spain: characterization of 10 novel mutations in the UROD gene.
  Br J Dermatol, 157, 501-507.  
15736160 G.Chaufan, M.M.Corvi, L.C.San Martín de Viale, M.L.Cárdenas, and M.d.e.l. .C.Ríos de Molina (2005).
Abnormal kinetic behavior of uroporphyrinogen decarboxylase obtained from rats with hexachlorobenzene-induced porphyria.
  J Biochem Mol Toxicol, 19, 19-24.  
15652607 R.Kauppinen (2005).
Porphyrias.
  Lancet, 365, 241-252.  
16026339 R.Nezamzadeh, A.Seubert, J.Pohlenz, and B.Brenig (2005).
Identification of a mutation in the ovine uroporphyrinogen decarboxylase (UROD) gene associated with a type of porphyria.
  Anim Genet, 36, 297-302.  
15630480 R.Pejchal, and M.L.Ludwig (2005).
Cobalamin-independent methionine synthase (MetE): a face-to-face double barrel that evolved by gene duplication.
  PLoS Biol, 3, e31.
PDB codes: 1t7l 1xdj 1xpg 1xr2
15491440 D.K.Armstrong, P.C.Sharpe, C.R.Chambers, S.D.Whatley, A.G.Roberts, and G.H.Elder (2004).
Hepatoerythropoietic porphyria: a missense mutation in the UROD gene is associated with mild disease and an unusual porphyrin excretion pattern.
  Br J Dermatol, 151, 920-923.  
15186324 P.Poblete-Gutiérrez, M.Mendez, T.Wiederholt, H.F.Merk, A.Fontanellas, C.Wolff, and J.Frank (2004).
The molecular basis of porphyria cutanea tarda in Chile: identification and functional characterization of mutations in the uroporphyrinogen decarboxylase gene.
  Exp Dermatol, 13, 372-379.  
15329673 P.R.Hall, R.Zheng, L.Antony, M.Pusztai-Carey, P.R.Carey, and V.C.Yee (2004).
Transcarboxylase 5S structures: assembly and catalytic mechanism of a multienzyme complex subunit.
  EMBO J, 23, 3621-3631.
PDB codes: 1rqb 1rqe 1rqh 1rr2 1s3h 1u5j
14633981 G.Layer, J.Moser, D.W.Heinz, D.Jahn, and W.D.Schubert (2003).
Crystal structure of coproporphyrinogen III oxidase reveals cofactor geometry of Radical SAM enzymes.
  EMBO J, 22, 6214-6224.
PDB code: 1olt
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
12957544 R.E.Steward, M.W.MacArthur, R.A.Laskowski, and J.M.Thornton (2003).
Molecular basis of inherited diseases: a structural perspective.
  Trends Genet, 19, 505-513.  
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.  
12220488 J.C.Evans, D.P.Huddler, J.Jiracek, C.Castro, N.S.Millian, T.A.Garrow, and M.L.Ludwig (2002).
Betaine-homocysteine methyltransferase: zinc in a distorted barrel.
  Structure, 10, 1159-1171.
PDB codes: 1lt7 1lt8
11863436 J.R.Tame, K.Namba, E.J.Dodson, and D.I.Roper (2002).
The crystal structure of HpcE, a bifunctional decarboxylase/isomerase with a multifunctional fold.
  Biochemistry, 41, 2982-2989.
PDB codes: 1gtt 1i7o
11679753 B.M.Martins, B.Grimm, H.P.Mock, G.Richter, R.Huber, and A.Messerschmidt (2001).
Tobacco uroporphyrinogen-III decarboxylase: characterization, crystallization and preliminary X-ray analysis.
  Acta Crystallogr D Biol Crystallogr, 57, 1709-1711.  
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
11134514 J.D.Phillips, L.K.Jackson, M.Bunting, M.R.Franklin, K.R.Thomas, J.E.Levy, N.C.Andrews, and J.P.Kushner (2001).
A mouse model of familial porphyria cutanea tarda.
  Proc Natl Acad Sci U S A, 98, 259-264.  
11069625 J.J.Brady, H.A.Jackson, A.G.Roberts, R.R.Morgan, S.D.Whatley, G.L.Rowlands, C.Darby, E.Shudell, R.Watson, J.Paiker, M.W.Worwood, and G.H.Elder (2000).
Co-inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of porphyria cutanea tarda.
  J Invest Dermatol, 115, 868-874.  
10477430 L.Christiansen, C.Ged, I.Hombrados, J.Brons-Poulsen, A.Fontanellas, H.de Verneuil, M.Hørder, and N.E.Petersen (1999).
Screening for mutations in the uroporphyrinogen decarboxylase gene using denaturing gradient gel electrophoresis. Identification and characterization of six novel mutations associated with familial PCT.
  Hum Mutat, 14, 222-232.  
9792863 M.Mendez, L.Sorkin, M.V.Rossetti, K.H.Astrin, A.M.del C Batlle, V.E.Parera, G.Aizencang, and R.J.Desnick (1998).
Familial porphyria cutanea tarda: characterization of seven novel uroporphyrinogen decarboxylase mutations and frequency of common hemochromatosis alleles.
  Am J Hum Genet, 63, 1363-1375.  
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.