title: Structure and control of pyridoxal phosphate dependent allosteric threonine deaminase.
abstract: 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.
authors.affiliation: University of Maryland, Biotechnology Institute, National Institute of Standards and Technology 9600 Gudelsky Drive, Rockville, Maryland 20850, USA. travis@dtg.nist.gov
authors.forename: D T
authors.initials: DT
authors.lastname: Gallagher
authors.forename: G L
authors.initials: GL
authors.lastname: Gilliland
authors.forename: G
authors.initials: G
authors.lastname: Xiao
authors.forename: J
authors.initials: J
authors.lastname: Zondlo
authors.forename: K E
authors.initials: KE
authors.lastname: Fisher
authors.forename: D
authors.initials: D
authors.lastname: Chinchilla
authors.forename: E
authors.initials: E
authors.lastname: Eisenstein
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology; D001665:Binding Sites / Q000502:physiology; D002237:Carbohydrate Dehydrogenases / Q000737:chemistry; D018360:Crystallography, X-Ray; D019281:Dimerization; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D050543:Phosphoglycerate Dehydrogenase; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011732:Pyridoxal Phosphate / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013913:Threonine Dehydratase / Q000737:chemistry*; D014367:Tryptophan Synthase / Q000737:chemistry; D014633:Valine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011732:Pyridoxal Phosphate; D002237:Carbohydrate Dehydrogenases; D050543:Phosphoglycerate Dehydrogenase; D014367:Tryptophan Synthase; D013913:Threonine Dehydratase; D014633:Valine