PDBsum entry 1r3n

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Hydrolase PDB id
Protein chains
(+ 2 more) 438 a.a. *
BIB ×8
_ZN ×16
Waters ×509
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of beta-alanine synthase from saccharomyces kluyveri
Structure: Beta-alanine synthase. Chain: a, b, c, d, e, f, g, h. Engineered: yes
Source: Lachancea kluyveri. Organism_taxid: 4934. Gene: pyd3. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
2.70Å     R-factor:   0.211     R-free:   0.266
Authors: S.Lundgren,Z.Gojkovic,J.Piskur,D.Dobritzsch
Key ref:
S.Lundgren et al. (2003). Yeast beta-alanine synthase shares a structural scaffold and origin with dizinc-dependent exopeptidases. J Biol Chem, 278, 51851-51862. PubMed id: 14534321 DOI: 10.1074/jbc.M308674200
02-Oct-03     Release date:   11-Nov-03    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q96W94  (Q96W94_LACKL) -  Beta-alanine synthase
455 a.a.
438 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Beta-ureidopropionase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: N-carbamoyl-beta-alanine + H2O = beta-alanine + CO2 + NH3
+ H(2)O
Bound ligand (Het Group name = BIB)
matches with 85.00% similarity
+ CO(2)
+ NH(3)
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  


DOI no: 10.1074/jbc.M308674200 J Biol Chem 278:51851-51862 (2003)
PubMed id: 14534321  
Yeast beta-alanine synthase shares a structural scaffold and origin with dizinc-dependent exopeptidases.
S.Lundgren, Z.Gojković, J.Piskur, D.Dobritzsch.
beta-Alanine synthase (beta AS) is the final enzyme of the reductive pyrimidine catabolic pathway, which is responsible for the breakdown of pyrimidine bases, including several anticancer drugs. In eukaryotes, beta ASs belong to two subfamilies, which exhibit a low degree of sequence similarity. We determined the structure of beta AS from Saccharomyces kluyveri to a resolution of 2.7 A. The subunit of the homodimeric enzyme consists of two domains: a larger catalytic domain with a dizinc metal center, which represents the active site of beta AS, and a smaller domain mediating the majority of the intersubunit contacts. Both domains exhibit a mixed alpha/beta-topology. Surprisingly, the observed high structural homology to a family of dizinc-dependent exopeptidases suggests that these two enzyme groups have a common origin. Alterations in the ligand composition of the metal-binding site can be explained as adjustments to the catalysis of a different reaction, the hydrolysis of an N-carbamyl bond by beta AS compared with the hydrolysis of a peptide bond by exopeptidases. In contrast, there is no resemblance to the three-dimensional structure of the functionally closely related N-carbamyl-d-amino acid amidohydrolases. Based on comparative structural analysis and observed deviations in the backbone conformations of the eight copies of the subunit in the asymmetric unit, we suggest that conformational changes occur during each catalytic cycle.
  Selected figure(s)  
Figure 2.
FIG. 2. Comparison of the subunit structures of dizinc-dependent exopeptidases and Sk AS. The color scheme for the latter is the same as described for Fig. 1a. For the exopeptidases, the secondary structure elements are shown in blue ( -strands) and red ( - and 3[10]-helices). The zinc ions are depicted as purple (for Sk AS) and blue (for exopeptidases) spheres.
Figure 4.
FIG. 4. Structure-based alignment of the sequences of Sk AS and dizinc-dependent exopeptidases. Row 1, Sk AS; row 2, SGAP; row 3; APAP; row 4, CPG2; row 5, PepV; row 6, PepT. The secondary structure elements (labeled as described for Fig. 1a) are indicated by arrows for -strands and boxes for - and 3[10]-helices, which are white for the catalytic domain and light blue for the dimerization domain of Sk AS. For the exopeptidases, only the sequences of the structurally aligned parts are shown (uppercase letters). Pink number signs indicate the zinc-coordinating residues. Amino acids labeled by boldface letters indicate sequence conservation in all structurally aligned sequence parts of exopeptidases. If the amino acid is also conserved in the sequence of Sk AS, the residue is marked additionally by pink background shading. Gray background shading indicates sequence conservation between Sk AS and any of the exopeptidases. For residues that are conserved and aligned only in some of the six proteins, the corresponding amino acid in the non-aligned proteins is given as a lowercase italic letter if its spatial position only barely does not fulfill the requirements defining structural alignment. A hyphen is used when the residue is not present at the same position due to either considerable differences in structure or deletions in the sequence. Dotted lines indicate the absence of the dimerization domain in SGAP and APAP.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 51851-51862) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19830420 S.Martínez-Rodríguez, A.I.Martínez-Gómez, F.Rodríguez-Vico, J.M.Clemente-Jiménez, and F.J.Las Heras-Vázquez (2010).
Carbamoylases: characteristics and applications in biotechnological processes.
  Appl Microbiol Biotechnol, 85, 441-458.  
19011069 A.I.Martínez-Gómez, S.Martínez-Rodríguez, J.Pozo-Dengra, D.Tessaro, S.Servi, J.M.Clemente-Jiménez, F.Rodríguez-Vico, and F.J.Las Heras-Vázquez (2009).
Potential application of N-carbamoyl-beta-alanine amidohydrolase from Agrobacterium tumefaciens C58 for beta-amino acid production.
  Appl Environ Microbiol, 75, 514-520.  
  19052368 S.Martínez-Rodríguez, A.García-Pino, F.J.Las Heras-Vázquez, J.M.Clemente-Jiménez, F.Rodríguez-Vico, R.Loris, J.M.García-Ruiz, and J.A.Gavira (2008).
Crystallization and preliminary crystallographic studies of the recombinant L-N-carbamoylase from Geobacillus stearothermophilus CECT43.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1135-1138.  
17355287 G.Andersen, B.Andersen, D.Dobritzsch, K.D.Schnackerz, and J.Piskur (2007).
A gene duplication led to specialized gamma-aminobutyrate and beta-alanine aminotransferase in yeast.
  FEBS J, 274, 1804-1817.  
  17909293 S.Lundgren, B.Andersen, J.Piskur, and D.Dobritzsch (2007).
Crystallization and preliminary X-ray data analysis of beta-alanine synthase from Drosophila melanogaster.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 874-877.  
15075270 J.Stolz, T.Caspari, A.M.Carr, and N.Sauer (2004).
Cell division defects of Schizosaccharomyces pombe liz1- mutants are caused by defects in pantothenate uptake.
  Eukaryot Cell, 3, 406-412.  
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.