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J Biol Chem. 2012 Dec 7;287(50):42333-43. doi: 10.1074/jbc.M112.397240. Epub 2012 Oct 9.

The last piece in the vitamin B1 biosynthesis puzzle: structural and functional insight into yeast 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P) synthase.

Author information

1
Department of Molecular Biology, University of Geneva, Geneva 1211, Switzerland.

Abstract

Vitamin B(1) is essential for all organisms being well recognized as a necessary cofactor for key metabolic pathways such as glycolysis, and was more recently implicated in DNA damage responses. Little is known about the enzyme responsible for the formation of the pyrimidine moiety (4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P) synthase). We report a structure-function study of the HMP-P synthase from yeast, THI5p. Our crystallographic structure shows that THI5p is a mix between periplasmic binding proteins and pyridoxal 5'-phosphate-dependent enzymes. Mutational and yeast complementation studies identify the key residues for HMP-P biosynthesis as well as the use of pyridoxal 5'-phosphate as a substrate rather than as a cofactor. Furthermore, we could show that iron binding to HMP-P synthase is essential for the reaction.

PMID:
23048037
PMCID:
PMC3516776
DOI:
10.1074/jbc.M112.397240
[Indexed for MEDLINE]
Free PMC Article

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