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The crystal structure of beta-alanine synthase from Drosophila melanogaster reveals a homooctameric helical turn-like assembly

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Author

  • Stina Lundgren
  • Bernhard Lohkamp
  • Birgit Andersen
  • Jure Piskur
  • Doreen Dobritzsch

Summary, in English

beta-Alanine synthase (PAS) is the third enzyme in the reductive pyrimidine catabolic pathway, which is responsible for the breakdown of the nucleotide bases uracil and thymine in higher organisms. It catalyzes the hydrolysis of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyrate to the corresponding beta-amino acids. beta ASs are grouped into two phylogenetically unrelated subfamilies, a general eukaryote one and a fungal one. To reveal the molecular architecture and understand the catalytic mechanism of the general eukaryote PAS subfamily, we determined the crystal structure of Drosophila melanogaster PAS to 2.8 angstrom resolution. It shows a homooctameric assembly of the enzyme in the shape of a left-handed helical turn, in which tightly packed dimeric units are related by 2-fold symmetry. Such an assembly would allow formation of higher oligomers by attachment of additional dimers on both ends. The subunit has a nitrilase-like fold and consists of a central beta-sandwich with a layer of alpha-helices packed against both sides. However, the core fold of the nitrilase superfamily enzymes is extended in D. melanogaster PAS by addition of several secondary structure elements at the N-terminus. The active site can be accessed from the solvent by a narrow channel and contains the triad of catalytic residues (Cys, Glu, and Lys) conserved in nitrilase-like enzymes.

Publishing year

2008

Language

English

Pages

1544-1559

Publication/Series

Journal of Molecular Biology

Volume

377

Issue

5

Document type

Journal article

Publisher

Elsevier

Topic

  • Biological Sciences

Keywords

  • crystallography
  • X-ray
  • quaternary structure
  • nitrilase
  • beta-alanine
  • amidohydrolase

Status

Published

ISBN/ISSN/Other

  • ISSN: 1089-8638