Suramin is a novel activator of PP5 and biphasically modulates S100-activated PP5 activity

Fuminori Yamaguchi, Sho Yamamura, Seiko Shimamoto, Hiroshi Tokumitsu, Masaaki Tokuda, Ryoji Kobayashi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Suramin is an activator of ryanodine receptors and competitively binds to the calmodulin-binding site. In addition, S100A1 and calmodulin compete for the same binding site on ryanodine receptors. We therefore studied the effects of suramin on protein phosphatase 5 (PP5) and S100-activated PP5. In the absence of S100 proteins, suramin bound to the tetratricopeptide repeat (TPR) domain of PP5 and activated the enzyme in a dose-dependent manner. In the presence of S100A2/Ca2+, lower concentrations of suramin dose-dependently inhibited PP5 activity as an S100 antagonist, whereas higher concentrations of suramin reactivated PP5. Although the C-terminal fragment of heat shock protein 90 (HspC90) also weakly activated PP5, the binding site of suramin and HspC90 may be different, and addition of suramin showed no clear effect on the phosphatase activity of PP5. Similar biphasic effects of suramin were observed with S100A1-, S100B- or S100P-activated PP5. However, the inhibitory effects of lower concentrations of suramin on S100A6-activated PP5 are weak and high concentrations of suramin further activated PP5. SPR and the cross-linking study showed inhibition of the interaction between S100 protein and PP5 by suramin. Our results revealed that suramin is a novel PP5 activator and modulates S100-activated PP5 activity by competitively binding to the TPR domain.

Original languageEnglish
Pages (from-to)237-247
Number of pages11
JournalApplied Biochemistry and Biotechnology
Volume172
Issue number1
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Keywords

  • Hsp90
  • Protein phosphatase 5
  • S100 protein
  • Suramin
  • Tetratricopeptide repeat

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology

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