Structural basis of charge transfer complex formation by riboflavin bound to 6,7-dimethyl-8-ribityllumazine synthase

Eur J Biochem. 2004 Aug;271(15):3208-14. doi: 10.1111/j.1432-1033.2004.04253.x.

Abstract

The amino acid residue tryptophan 27 of 6,7-dimethyl-8-ribityllumazine synthase of the yeast Schizosaccharomyces pombe was replaced by tyrosine. The structures of the W27Y mutant protein in complex with riboflavin, the substrate analogue 5-nitroso-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, and the product analogue 6-carboxyethyl-7-oxo-8-ribityllumazine, were determined by X-ray crystallography at resolutions of 2.7-2.8 A. Whereas the indole system of W27 forms a coplanar pi-complex with riboflavin, the corresponding phenyl ring in the W27Y mutant establishes only peripheral contact with the heterocyclic ring system of the bound riboflavin. These findings provide an explanation for the absence of the long wavelength shift in optical absorption spectra of riboflavin bound to the mutant enzyme. The structures of the mutants are important tools for the interpretation of the unusual physical properties of riboflavin in complex with lumazine synthase.

Publication types

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

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Models, Molecular
  • Molecular Structure
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / chemistry*
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Mutation / genetics
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Riboflavin / chemistry
  • Riboflavin / metabolism*
  • Schizosaccharomyces / enzymology*
  • Schizosaccharomyces / genetics
  • Structure-Activity Relationship
  • Tryptophan / genetics
  • Tryptophan / metabolism

Substances

  • Multienzyme Complexes
  • 6,7-dimethyl-8-ribityllumazine synthase
  • Tryptophan
  • Riboflavin