4h6d

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

Structural highlights

4h6d is a 8 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.9Å
Ligands:PLP
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

THI5_YEAST Proposed biosynthetic enzyme involved in pyrimidine biosynthesis pathway above the hydroxymethyl-pyrimidine precursor leading to the thiamine moiety.[1]

Publication Abstract from PubMed

Vitamin B1 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 (HMP-P synthase). We report a structure-function study of the HMP-P synthase from yeast, THI5p. Our crystallographic structure shows that the THI5p is a mix between periplasmic binding proteins and pyridoxal 5'-phosphate (PLP) dependent enzymes. Mutational and yeast complementation studies identify the key residues for HMP-P biosynthesis and offers unprecedented insights into the use of PLP as a substrate rather than as a cofactor, the requirement of iron and more generally into the HMP-P synthase reaction mechanism.

The last piece in the vitamin B1 biosynthesis puzzle: Structural and functional insight into yeast HMP-P synthase.,Coquille S, Roux C, Fitzpatrick TB, Thore S J Biol Chem. 2012 Oct 9. PMID:23048037[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. Wightman R, Meacock PA. The THI5 gene family of Saccharomyces cerevisiae: distribution of homologues among the hemiascomycetes and functional redundancy in the aerobic biosynthesis of thiamin from pyridoxine. Microbiology. 2003 Jun;149(Pt 6):1447-60. PMID:12777485
  2. Coquille S, Roux C, Fitzpatrick TB, Thore S. The last piece in the vitamin B1 biosynthesis puzzle: Structural and functional insight into yeast HMP-P synthase. J Biol Chem. 2012 Oct 9. PMID:23048037 doi:http://dx.doi.org/10.1074/jbc.M112.397240

Contents


PDB ID 4h6d

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