A heterodimer of human 3'-phospho-adenosine-5'-phosphosulphate (PAPS) synthases is a new sulphate activating complex

Daniel Grum, Johannes van den Boom, Daniel Neumann, Anja Matena, Nina M Link, Jonathan W Mueller

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

3'-Phospho-adenosine-5'-phosphosulphate (PAPS) synthases are fundamental to mammalian sulphate metabolism. These enzymes have recently been linked to a rising number of human diseases. Despite many studies, it is not yet understood how the mammalian PAPS synthases 1 and 2 interact with each other. We provide first evidence for heterodimerisation of these two enzymes by pull-down assays and Förster resonance energy transfer (FRET) measurements. Kinetics of dimer dissociation/association indicates that these heterodimers form as soon as PAPSS1 and -S2 encounter each other in solution. Affinity of the homo- and heterodimers were found to be in the low nanomolar range using anisotropy measurements employing proteins labelled with the fluorescent dye IAEDANS that--in spite of its low quantum yield--is well suited for anisotropy due to its large Stokes shift. Within its kinase domain, the PAPS synthase heterodimer displays similar substrate inhibition by adenosine-5'-phosphosulphate (APS) as the homodimers. Due to divergent catalytic efficacies of PAPSS1 and -S2, the heterodimer might be a way of regulating PAPS synthase function within mammalian cells.

Original languageEnglish
Pages (from-to)420-5
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume395
Issue number3
DOIs
Publication statusPublished - 7 May 2010

Keywords

  • Anisotropy
  • Enzyme Activation
  • Humans
  • Isoenzymes
  • Kinetics
  • Multienzyme Complexes
  • Protein Multimerization
  • Sulfate Adenylyltransferase
  • Sulfates

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