Structural insights into the function of the thiamin biosynthetic enzyme Thi4 from Saccharomyces cerevisiae

Biochemistry. 2006 Sep 19;45(37):11061-70. doi: 10.1021/bi061025z.


The structure of thiazole synthase (Thi4) from Saccharomyces cerevisiae was determined to 1.8 A resolution. Thi4 exists as an octamer with two monomers in the asymmetric unit. The structure reveals the presence of a tightly bound adenosine diphospho-5-(beta-ethyl)-4-methylthiazole-2-carboxylic acid at the active site. The isolation of this reaction product identifies NAD as the most likely precursor and provides the first mechanistic insights into the biosynthesis of the thiamin thiazole in eukaryotes. Additionally, the Thi4 structure reveals the first protein structure with a GR(2) domain that binds NAD instead of FAD, raising interesting questions about how this protein evolved from a flavoenzyme to a NAD binding enzyme.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Flavin-Adenine Dinucleotide / chemistry
  • Flavin-Adenine Dinucleotide / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • NAD / chemistry
  • NAD / metabolism
  • Protein Conformation
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Thiamine / biosynthesis*
  • Thiamine / chemistry


  • Saccharomyces cerevisiae Proteins
  • THI4 protein, S cerevisiae
  • NAD
  • Flavin-Adenine Dinucleotide
  • Thiamine

Associated data

  • PDB/2GJC