4H6D

Crystal structure of PLP-soaked HMP synthase Thi5 from S. cerevisiae

Summary for 4H6D

• Entry DOI: 10.2210/pdb4h6d/pdb
• Related: 4H65 4H67
• Descriptor: Pyrimidine precursor biosynthesis enzyme THI5, PYRIDOXAL-5'-PHOSPHATE (2 entities in total)
• Functional Keywords: synthase, transferase
• Biological source: Saccharomyces cerevisiae (yeast)
• Total number of polymer chains: 8
• Total formula weight: 316313.26

Authors

Coquille, S.C.,Roux, C.,Fitzpatrick, T.,Thore, S. (deposition date: 2012-09-19, release date: 2012-10-17, Last modification date: 2023-09-20)

Primary citation

Coquille, S.,Roux, C.,Fitzpatrick, T.B.,Thore, S.
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.
J.Biol.Chem., 287:42333-42343, 2012

PubMed 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.

PubMed: 23048037
DOI: 10.1074/jbc.M112.397240

Experimental method

X-RAY DIFFRACTION (2.9 Å)