X-ray crystal structure of Saccharomyces cerevisiae Pdx1 provides insights into the oligomeric nature of PLP synthases

FEBS Lett. 2009 Jul 7;583(13):2179-86. doi: 10.1016/j.febslet.2009.06.009. Epub 2009 Jun 11.

Abstract

The universal enzymatic cofactor vitamin B6 can be synthesized as pyridoxal 5-phosphate (PLP) by the glutamine amidotransferase Pdx1. We show that Saccharomyces cerevisiae Pdx1 is hexameric by analytical ultracentrifugation and by crystallographic 3D structure determination. Bacterial homologues were previously reported to exist in hexamer:dodecamer equilibrium. A small sequence insertion found in yeast Pdx1 elevates the dodecamer dissociation constant when introduced into Bacillus subtilis Pdx1. Further, we demonstrate that the yeast Pdx1 C-terminus contacts an adjacent subunit, and deletion of this segment decreases enzymatic activity 3.5-fold, suggesting a role in catalysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus subtilis / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Catalysis
  • Crystallography, X-Ray
  • Glutaminase / chemistry*
  • Glutaminase / metabolism
  • Models, Molecular
  • Protein Conformation
  • Protein Folding
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Pyruvate Dehydrogenase Complex / chemistry*
  • Pyruvate Dehydrogenase Complex / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Substrate Specificity

Substances

  • Bacterial Proteins
  • PDX1 protein, S cerevisiae
  • Protein Subunits
  • Pyruvate Dehydrogenase Complex
  • Saccharomyces cerevisiae Proteins
  • Glutaminase