Defining the structural requirements for ribose 5-phosphate-binding and intersubunit cross-talk of the malarial pyridoxal 5-phosphate synthase

FEBS Lett. 2010 Oct 8;584(19):4169-74. doi: 10.1016/j.febslet.2010.09.013. Epub 2010 Sep 17.

Abstract

Most organisms synthesise the B(6) vitamer pyridoxal 5-phosphate (PLP) via the glutamine amidotransferase PLP synthase, a large enzyme complex of 12 Pdx1 synthase subunits with up to 12 Pdx2 glutaminase subunits attached. Deletion analysis revealed that the C-terminus has four distinct functionalities: assembly of the Pdx1 monomers, binding of the pentose substrate (ribose 5-phosphate), formation of the reaction intermediate I(320), and finally PLP synthesis. Deletions of distinct C-terminal regions distinguish between these individual functions. PLP formation is the only function that is conferred to the enzyme by the C-terminus acting in trans, explaining the cooperative nature of the complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • DNA, Protozoan / genetics
  • Glutaminase / chemistry*
  • Glutaminase / genetics
  • Glutaminase / metabolism*
  • Kinetics
  • Models, Molecular
  • Molecular Sequence Data
  • Multiprotein Complexes
  • Plasmodium falciparum / enzymology*
  • Plasmodium falciparum / genetics
  • Protein Subunits
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Pyridoxal Phosphate / biosynthesis*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Ribosemonophosphates / metabolism*
  • Sequence Deletion

Substances

  • DNA, Protozoan
  • Multiprotein Complexes
  • Protein Subunits
  • Protozoan Proteins
  • Recombinant Proteins
  • Ribosemonophosphates
  • ribose-5-phosphate
  • Pyridoxal Phosphate
  • Glutaminase