title: Multistate binding in pyridoxine 5'-phosphate synthase: 1.96 A crystal structure in complex with 1-deoxy-D-xylulose phosphate.
abstract: We report the 1.96 A crystal structure of pyridoxine 5'-phosphate synthase (PdxJ) in complex with 1-deoxy-D-xylulose phosphate (dXP). The octameric enzyme possesses eight distinct binding sites, and three different binding states are observed. The observation of these three states supports a mechanism in which precise conformational changes of a peptide loop and groups of active site residues modulate binding and specificity. The differences in protein conformation when one or two substrates are bound can be correlated with a condensation mechanism that leads productively to the formation of pyridoxine 5'-phosphate (PNP). "Snapshots" of the progression from the apo form to a singly occupied "transitional binding" state and, subsequently, to a fully occupied, reactive state are revealed and indicate how the enzyme structure can be related to a plausible catalytic mechanism and, moreover, to favorable energetics of reaction.
authors.affiliation: Molecular Biology, Cell Biology, and Biochemistry Department, Brown University, Box G-J2, Providence, RI 02912-9108, USA. Joanne_Yeh@brown.edu
authors.forename: Joanne I
authors.initials: JI
authors.lastname: Yeh
authors.forename: Shoucheng
authors.initials: S
authors.lastname: Du
authors.forename: Ehmke
authors.initials: E
authors.lastname: Pohl
authors.forename: David E
authors.initials: DE
authors.lastname: Cane
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D002151:Calorimetry; D002384:Catalysis; D003460:Crystallization; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins; D008025:Ligases; D010428:Pentosephosphates / Q000737:chemistry*; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D011732:Pyridoxal Phosphate / Q000737:chemistry; D013379:Substrate Specificity
chemical_list: C109460:1-deoxylulose 5-phosphate; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C098854:PdxJ protein, E coli; D010428:Pentosephosphates; D011732:Pyridoxal Phosphate; C027138:pyridoxine phosphate phosphatase; D010744:Phosphoric Monoester Hydrolases; D008025:Ligases