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PDBsum entry 2fty

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protein metals Protein-protein interface(s) links
Hydrolase PDB id
2fty
Jmol
Contents
Protein chains
532 a.a. *
Metals
_ZN ×8
Waters ×681
* Residue conservation analysis
PDB id:
2fty
Name: Hydrolase
Title: Crystal structure of dihydropyrimidinase from saccharomyces
Structure: Dihydropyrimidinase. Chain: a, b, c, d. Engineered: yes
Source: Lachancea kluyveri. Organism_taxid: 4934. Gene: pyd2. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Tetramer (from PQS)
Resolution:
2.40Å     R-factor:   0.220     R-free:   0.274
Authors: D.Dobritzsch,B.Lohkamp
Key ref:
B.Lohkamp et al. (2006). The crystal structures of dihydropyrimidinases reaffirm the close relationship between cyclic amidohydrolases and explain their substrate specificity. J Biol Chem, 281, 13762-13776. PubMed id: 16517602 DOI: 10.1074/jbc.M513266200
Date:
25-Jan-06     Release date:   14-Mar-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9P903  (DPYS_LACKL) -  Dihydropyrimidinase
Seq:
Struc:
 
Seq:
Struc:
542 a.a.
532 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.3.5.2.2  - Dihydropyrimidinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 5,6-dihydrouracil + H2O = 3-ureidopropanoate
5,6-dihydrouracil
+ H(2)O
= 3-ureidopropanoate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     hydrolase activity     4 terms  

 

 
    Added reference    
 
 
DOI no: 10.1074/jbc.M513266200 J Biol Chem 281:13762-13776 (2006)
PubMed id: 16517602  
 
 
The crystal structures of dihydropyrimidinases reaffirm the close relationship between cyclic amidohydrolases and explain their substrate specificity.
B.Lohkamp, B.Andersen, J.Piskur, D.Dobritzsch.
 
  ABSTRACT  
 
In eukaryotes, dihydropyrimidinase catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Here we describe the three-dimensional structures of dihydropyrimidinase from two eukaryotes, the yeast Saccharomyces kluyveri and the slime mold Dictyostelium discoideum, determined and refined to 2.4 and 2.05 angstroms, respectively. Both enzymes have a (beta/alpha)8-barrel structural core embedding the catalytic di-zinc center, which is accompanied by a smaller beta-sandwich domain. Despite loop-forming insertions in the sequence of the yeast enzyme, the overall structures and architectures of the active sites of the dihydropyrimidinases are strikingly similar to each other, as well as to those of hydantoinases, dihydroorotases, and other members of the amidohydrolase superfamily of enzymes. However, formation of the physiologically relevant tetramer shows subtle but nonetheless significant differences. The extension of one of the sheets of the beta-sandwich domain across a subunit-subunit interface in yeast dihydropyrimidinase underlines its closer evolutionary relationship to hydantoinases, whereas the slime mold enzyme shows higher similarity to the noncatalytic collapsin-response mediator proteins involved in neuron development. Catalysis is expected to follow a dihydroorotase-like mechanism but in the opposite direction and with a different substrate. Complexes with dihydrouracil and N-carbamyl-beta-alanine obtained for the yeast dihydropyrimidinase reveal the mode of substrate and product binding and allow conclusions about what determines substrate specificity, stereoselectivity, and the reaction direction among cyclic amidohydrolases.
 
  Selected figure(s)  
 
Figure 1.
FIGURE 1. Subunit structures. a, stereo view of the subunit of ^SkDHPase. The following color coding is used for the secondary structure elements: green and dark green, barrel strands and helices, respectively; blue and light blue, strands of the larger and smaller sheets of the -sandwich domain, respectively; yellow, additional -strands; orange and dark orange, additional - and 3[10]-helices, respectively. Spheres in magenta represent the zinc ions of the metal center. b, stereo view of the subunit of ^DdDHPase. The same color coding as in a is used. c, stereo view of the superimposed subunits of ^SkDHPase (light blue), ^DdDHPase (blue), CRMP1 (gold), and ^B9D-Hyd (magenta). The orientation is changed for better visualization of the structural differences, especially at the C terminus, and is related to that from a and b by a 45° upward rotation around a horizontal axis lying within the paper plane.
Figure 3.
FIGURE 3. Structures of the tetramers showing the intersubunit interfaces. a, tetramer of ^SkDHPase in two orientations related by a 90° rotation around a 2-fold axis lying within the paper plane (as indicated), with subunits A, B, C, and D shown in gold, magenta, blue, and light green. b, corresponding view of the ^DdDHPase tetramer. Here the subunits are shown in yellow (A), red (B), light blue (C), and green (D). The rigid body movement of the dimer pairs in relation to the corresponding pairs in ^SkDHPase is indicated by an arrow. c, tetramer of ^B9D-Hyd, with the subunits colored in correspondence to ^SkDHPase. d, tetramer of CRMP1. The subunit color code corresponds to that of ^DdDHPase.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 13762-13776) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20676924 C.C.Wang, H.W.Tsau, W.T.Chen, and C.Y.Huang (2010).
Identification and characterization of a putative dihydroorotase, KPN01074, from Klebsiella pneumoniae.
  Protein J, 29, 445-452.  
19649633 J.Fidlerova, P.Kleiblova, M.Bilek, S.Kormunda, Z.Formankova, J.Novotny, and Z.Kleibl (2010).
Contribution of dihydropyrimidinase gene alterations to the development of serious toxicity in fluoropyrimidine-treated cancer patients.
  Cancer Chemother Pharmacol, 65, 661-669.  
19490017 Y.Cai, P.Trodler, S.Jiang, W.Zhang, Y.Wu, Y.Lu, S.Yang, and W.Jiang (2009).
Isolation and molecular characterization of a novel D-hydantoinase from Jannaschia sp. CCS1.
  FEBS J, 276, 3575-3588.  
18556813 X.Y.Zhang, L.X.Niu, Y.W.Shi, and J.M.Yuan (2008).
The flexibility of the non-conservative region at the C terminus of D-hydantoinase from Pseudomonas putida YZ-26 is extremely limited.
  Appl Biochem Biotechnol, 144, 237-247.  
17506874 J.D.Burman, C.E.Stevenson, R.G.Sawers, and D.M.Lawson (2007).
The crystal structure of Escherichia coli TdcF, a member of the highly conserved YjgF/YER057c/UK114 family.
  BMC Struct Biol, 7, 30.
PDB codes: 2uyj 2uyk 2uyn 2uyp
18251875 M.J.Raso, M.Pineda, and P.Piedras (2007).
Tissue abundance and characterization of two purified proteins with allantoinase activity from French bean (Phaseolus vulgaris).
  Physiol Plant, 131, 355-366.  
17250651 P.Stenmark, D.Ogg, S.Flodin, A.Flores, T.Kotenyova, T.Nyman, P.Nordlund, and P.Kursula (2007).
The structure of human collapsin response mediator protein 2, a regulator of axonal growth.
  J Neurochem, 101, 906-917.
PDB code: 2gse
  17142902 S.Martínez-Rodríguez, L.A.González-Ramírez, J.M.Clemente-Jiménez, F.Rodríguez-Vico, F.J.Las Heras-Vázquez, J.A.Gavira, and J.M.García-Ruíz (2006).
Crystallization and preliminary crystallographic studies of the recombinant dihydropyrimidinase from Sinorhizobium meliloti CECT4114.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 1223-1226.  
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.