title: Structure and function of threonine synthase from yeast.
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.
authors.affiliation: Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, am Klopferspitz 18A, Martinsried 82152, Germany.
authors.forename: Marta
authors.initials: M
authors.lastname: Garrido-Franco
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehlert
authors.forename: Albrecht
authors.initials: A
authors.lastname: Messerschmidt
authors.forename: Snezan
authors.initials: S
authors.lastname: Marinkovic'
authors.forename: Robert
authors.initials: R
authors.lastname: Huber
authors.forename: Bernd
authors.initials: B
authors.lastname: Laber
authors.forename: Gleb P
authors.initials: GP
authors.lastname: Bourenkov
authors.forename: Tim
authors.initials: T
authors.lastname: Clausen
mesh_terms: D001665:Binding Sites; D019757:Carbon-Oxygen Lyases / Q000737:chemistry* / Q000502:physiology*; D002384:Catalysis; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D019757:Carbon-Oxygen Lyases; C023160:threonine synthase