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

Lundgren, Stina; Lohkamp, Bernhard; Andersen, Birgit LU ; Piskur, Jure LU and Dobritzsch, Doreen (2008) In Journal of Molecular Biology 377(5). p.1544-1559
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
crystallography, X-ray, quaternary structure, nitrilase, beta-alanine, amidohydrolase
in
Journal of Molecular Biology
volume
377
issue
5
pages
1544 - 1559
publisher
Elsevier
external identifiers
  • wos:000254979500020
  • scopus:40849116037
ISSN
1089-8638
DOI
10.1016/j.jmb.2008.02.011
language
English
LU publication?
yes
id
3f6001a9-5ab6-4382-901c-a8ede3021662 (old id 1206338)
date added to LUP
2008-09-19 12:38:55
date last changed
2017-05-28 04:02:36
@article{3f6001a9-5ab6-4382-901c-a8ede3021662,
  abstract     = {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.},
  author       = {Lundgren, Stina and Lohkamp, Bernhard and Andersen, Birgit and Piskur, Jure and Dobritzsch, Doreen},
  issn         = {1089-8638},
  keyword      = {crystallography,X-ray,quaternary structure,nitrilase,beta-alanine,amidohydrolase},
  language     = {eng},
  number       = {5},
  pages        = {1544--1559},
  publisher    = {Elsevier},
  series       = {Journal of Molecular Biology},
  title        = {The crystal structure of beta-alanine synthase from Drosophila melanogaster reveals a homooctameric helical turn-like assembly},
  url          = {http://dx.doi.org/10.1016/j.jmb.2008.02.011},
  volume       = {377},
  year         = {2008},
}