Structure and function of threonine synthase from yeast

J Biol Chem. 2002 Apr 5;277(14):12396-405. doi: 10.1074/jbc.M108734200. Epub 2001 Dec 26.

Abstract

Threonine synthase catalyzes the final step of threonine biosynthesis, the pyridoxal 5'-phosphate (PLP)-dependent conversion of O-phosphohomoserine into threonine and inorganic phosphate. Threonine is an essential nutrient for mammals, and its biosynthetic machinery is restricted to bacteria, plants, and fungi; therefore, threonine synthase represents an interesting pharmaceutical target. The crystal structure of threonine synthase from Saccharomyces cerevisiae has been solved at 2.7 A resolution using multiwavelength anomalous diffraction. The structure reveals a monomer as active unit, which is subdivided into three distinct domains: a small N-terminal domain, a PLP-binding domain that covalently anchors the cofactor and a so-called large domain, which contains the main of the protein body. All three domains show the typical open alpha/beta architecture. The cofactor is bound at the interface of all three domains, buried deeply within a wide canyon that penetrates the whole molecule. Based on structural alignments with related enzymes, an enzyme-substrate complex was modeled into the active site of yeast threonine synthase, which revealed essentials for substrate binding and catalysis. Furthermore, the comparison with related enzymes of the beta-family of PLP-dependent enzymes indicated structural determinants of the oligomeric state and thus rationalized for the first time how a PLP enzyme acts in monomeric form.

MeSH terms

  • Binding Sites
  • Carbon-Oxygen Lyases / chemistry*
  • Carbon-Oxygen Lyases / physiology*
  • Catalysis
  • Crystallography, X-Ray
  • Escherichia coli / metabolism
  • Kinetics
  • Models, Chemical
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / enzymology*
  • Structure-Activity Relationship

Substances

  • Carbon-Oxygen Lyases
  • threonine synthase

Associated data

  • PDB/1KL7