Multistate binding in pyridoxine 5'-phosphate synthase: 1.96 A crystal structure in complex with 1-deoxy-D-xylulose phosphate

Biochemistry. 2002 Oct 1;41(39):11649-57. doi: 10.1021/bi026292t.

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.

Publication types

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

MeSH terms

  • Bacterial Proteins / chemistry*
  • Binding Sites
  • Calorimetry
  • Catalysis
  • Crystallization
  • Crystallography, X-Ray
  • Escherichia coli Proteins*
  • Ligases*
  • Pentosephosphates / chemistry*
  • Phosphoric Monoester Hydrolases / chemistry*
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Pyridoxal Phosphate / chemistry
  • Substrate Specificity

Substances

  • 1-deoxylulose 5-phosphate
  • Bacterial Proteins
  • Escherichia coli Proteins
  • PdxJ protein, E coli
  • Pentosephosphates
  • Pyridoxal Phosphate
  • pyridoxine phosphate phosphatase
  • Phosphoric Monoester Hydrolases
  • Ligases