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Oxidoreductase PDB id
1f76
Jmol
Contents
Protein chains
336 a.a. *
Ligands
FMN ×4
ORO ×3
FMT ×8
Waters ×1043
* Residue conservation analysis
PDB id:
1f76
Name: Oxidoreductase
Title: Escherichia coli dihydroorotate dehydrogenase
Structure: Dihydroorotate dehydrogenase. Chain: a, b, d, e. Engineered: yes
Source: Bacteria. Eubacteria. Organism_taxid: 2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.50Å     R-factor:   0.177     R-free:   0.217
Authors: S.Norager,K.F.Jensen,O.Bjornberg,S.Larsen
Key ref:
S.Nørager et al. (2002). E. coli dihydroorotate dehydrogenase reveals structural and functional distinctions between different classes of dihydroorotate dehydrogenases. Structure, 10, 1211-1223. PubMed id: 12220493 DOI: 10.1016/S0969-2126(02)00831-6
Date:
26-Jun-00     Release date:   16-Oct-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0A7E1  (PYRD_ECOLI) -  Dihydroorotate dehydrogenase (quinone)
Seq:
Struc: 		336 a.a.
336 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.3.5.2  - Dihydroorotate dehydrogenase (quinone).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (S)-dihydroorotate + a quinone = orotate + a quinol
(S)-dihydroorotate
Bound ligand (Het Group name = ORO)
corresponds exactly 		+ quinone
 = orotate
 + quinol
      Cofactor: FMN
FMN
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   2 terms 
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(02)00831-6 Structure 10:1211-1223 (2002)
PubMed id: 12220493  
 
 
E. coli dihydroorotate dehydrogenase reveals structural and functional distinctions between different classes of dihydroorotate dehydrogenases.
S.Nørager, K.F.Jensen, O.Björnberg, S.Larsen.
 
  ABSTRACT  
 
The flavoenzymes dihydroorotate dehydrogenases (DHODs) catalyze the fourth and only redox step in the de novo biosynthesis of UMP. Enzymes belonging to class 2, according to their amino acid sequence, are characterized by having a serine residue as the catalytic base and a longer N terminus. The structure of class 2 E. coli DHOD, determined by MAD phasing, showed that the N-terminal extension forms a separate domain. The catalytic serine residue has an environment differing from the equivalent cysteine in class 1 DHODs. Significant differences between the two classes of DHODs were identified by comparison of the E. coli DHOD with the other known DHOD structures, and differences with the class 2 human DHOD explain the variation in their inhibitors.
 
  Selected figure(s)  
 
Figure 7.
Figure 7. Mechanism of the First Half-Reaction Step Common for All DHODsSchematic drawing of the proposed reaction mechanism for the first half reaction, the oxidation of DHO to orotate. Events observed only in the class 1B (DHODB) structure, blue; H bonds observed only in class 2 (DHODC) and class 1A (DHODA), red.
 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 1211-1223) copyright 2002.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20484676 K.Möbius, R.Arias-Cartin, D.Breckau, A.L.Hännig, K.Riedmann, R.Biedendieck, S.Schröder, D.Becher, A.Magalon, J.Moser, M.Jahn, and D.Jahn (2010).
Heme biosynthesis is coupled to electron transport chains for energy generation.
  Proc Natl Acad Sci U S A, 107, 10436-10441.  
  20334617 M.A.Phillips, and P.K.Rathod (2010).
Plasmodium dihydroorotate dehydrogenase: a promising target for novel anti-malarial chemotherapy.
  Infect Disord Drug Targets, 10, 226-239.  
19530672 R.L.Fagan, and B.A.Palfey (2009).
Roles in binding and chemistry for conserved active site residues in the class 2 dihydroorotate dehydrogenase from Escherichia coli.
  Biochemistry, 48, 7169-7178.  
19694481 R.L.Kow, J.R.Whicher, C.A.McDonald, B.A.Palfey, and R.L.Fagan (2009).
Disruption of the proton relay network in the class 2 dihydroorotate dehydrogenase from Escherichia coli.
  Biochemistry, 48, 9801-9809.  
18225919 N.A.Malmquist, R.Gujjar, P.K.Rathod, and M.A.Phillips (2008).
Analysis of flavin oxidation and electron-transfer inhibition in Plasmodium falciparum dihydroorotate dehydrogenase.
  Biochemistry, 47, 2466-2475.  
17993483 S.G.Couto, M.C.Nonato, and A.J.Costa-Filho (2008).
Defects in vesicle core induced by escherichia coli dihydroorotate dehydrogenase.
  Biophys J, 94, 1746-1753.  
17369345 E.Zameitat, G.Freymark, C.D.Dietz, M.Löffler, and M.Bölker (2007).
Functional expression of human dihydroorotate dehydrogenase (DHODH) in pyr4 mutants of ustilago maydis allows target validation of DHODH inhibitors in vivo.
  Appl Environ Microbiol, 73, 3371-3379.  
17329250 N.A.Malmquist, J.Baldwin, and M.A.Phillips (2007).
Detergent-dependent kinetics of truncated Plasmodium falciparum dihydroorotate dehydrogenase.
  J Biol Chem, 282, 12678-12686.  
16510978 D.E.Hurt, J.Widom, and J.Clardy (2006).
Structure of Plasmodium falciparum dihydroorotate dehydrogenase with a bound inhibitor.
  Acta Crystallogr D Biol Crystallogr, 62, 312-323.
PDB code: 1tv5
16774642 E.Zameitat, Z.Gojković, W.Knecht, J.Piskur, and M.Löffler (2006).
Biochemical characterization of recombinant dihydroorotate dehydrogenase from the opportunistic pathogenic yeast Candida albicans.
  FEBS J, 273, 3183-3191.  
16624811 J.P.Combe, J.Basran, P.Hothi, D.Leys, S.E.Rigby, A.W.Munro, and N.S.Scrutton (2006).
Lys-D48 is required for charge stabilization, rapid flavin reduction, and internal electron transfer in the catalytic cycle of dihydroorotate dehydrogenase B of Lactococcus lactis.
  J Biol Chem, 281, 17977-17988.  
15044733 M.Hansen, J.Le Nours, E.Johansson, T.Antal, A.Ullrich, M.Löffler, and S.Larsen (2004).
Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain.
  Protein Sci, 13, 1031-1042.
PDB codes: 1uum 1uuo
12732650 S.Nørager, S.Arent, O.Björnberg, M.Ottosen, L.Lo Leggio, K.F.Jensen, and S.Larsen (2003).
Lactococcus lactis dihydroorotate dehydrogenase A mutants reveal important facets of the enzymatic function.
  J Biol Chem, 278, 28812-28822.
PDB codes: 1jqv 1jqx 1jrb 1jrc 1jub 1jue 1ovd
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.