Structure and control of pyridoxal phosphate dependent allosteric threonine deaminase

Structure. 1998 Apr 15;6(4):465-75. doi: 10.1016/s0969-2126(98)00048-3.


Background: Feedback inhibition of biosynthetic threonine deaminase (TD) from Escherichia coli provided one of the earliest examples of protein-based metabolic regulation. Isoleucine, the pathway end-product, and valine, the product of a parallel pathway, serve as allosteric inhibitor and activator, respectively. This enzyme is thus a useful model system for studying the structural basis of allosteric control mechanisms.

Results: We report the crystal structure of TD at 2.8 A resolution. The tetramer has 222 symmetry, with C-terminal regulatory domains projecting out from a core of catalytic PLP-containing N-terminal domains. The subunits, and especially the regulatory domains, associate extensively to form dimers, which associate less extensively to form the tetramer. Within the dimer, each monomer twists approximately 150 degrees around a thin neck between the domains to place its catalytic domain adjacent to the regulatory domain of the other subunit.

Conclusions: The structure of TD and its comparison with related structures and other data lead to the tentative identification of the regulatory binding site and revealed several implications for the allosteric mechanism. This work prepares the way for detailed structure/function studies of the complex allosteric behaviour of this enzyme.

Publication types

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

MeSH terms

  • Allosteric Regulation / physiology
  • Binding Sites / physiology
  • Carbohydrate Dehydrogenases / chemistry
  • Crystallography, X-Ray
  • Dimerization
  • Enzyme Activation / physiology
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli / enzymology*
  • Hydrogen Bonding
  • Models, Molecular
  • Phosphoglycerate Dehydrogenase
  • Protein Conformation
  • Protein Structure, Secondary
  • Pyridoxal Phosphate / chemistry*
  • Structure-Activity Relationship
  • Threonine Dehydratase / chemistry*
  • Tryptophan Synthase / chemistry
  • Valine / pharmacology


  • Enzyme Inhibitors
  • Pyridoxal Phosphate
  • Carbohydrate Dehydrogenases
  • Phosphoglycerate Dehydrogenase
  • Tryptophan Synthase
  • Threonine Dehydratase
  • Valine

Associated data

  • PDB/1TDJ