A Recruited Protease is Involved in Catabolism of Pyrimidines

Birgit Andersen, Stina Lundgren, Doreen Dobritzsch, Jure Piškur

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

In nature, the same biochemical reaction can be catalyzed by enzymes having fundamentally different folds, reaction mechanisms and origins. For example, the third step of the reductive catabolism of pyrimidines, the conversion of N-carbamyl-β-alanine to β-alanine, is catalyzed by two β-alanine synthase (βASase, EC 3.5.1.6) subfamilies. We show that the “prototype” eukaryote βASases, such as those from Drosophila melanogaster and Arabidopsis thaliana, are relatively efficient in the conversion of N-carbamyl-βA compared with a representative of fungal βASases, the yeast Saccharomyces kluyveri βASase, which has a high Km value (71 mM). S. kluyveri βASase is specifically inhibited by dipeptides and tripeptides, and the apparent Ki value of glycyl-glycine is in the same range as the substrate Km. We show that this inhibitor binds to the enzyme active center in a similar way as the substrate. The observed structural similarities and inhibition behavior, as well as the phylogenetic relationship, suggest that the ancestor of the fungal βASase was a protease that had modified its profession and become involved in the metabolism of nucleic acid precursors.
Original languageEnglish
JournalJournal of Molecular Biology
Volume379
Issue number2
Pages (from-to)243-250
ISSN0022-2836
DOIs
Publication statusPublished - 2008
Externally publishedYes

Keywords

  • nucleic acid precursors
  • β-alanine synthase
  • protease
  • structure–function relationship
  • protein evolution

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