Enzyme-substrate interactions revealed by the crystal structures of the archaeal Sulfolobus PTP-fold phosphatase and its phosphopeptide complexes

Hsing Mao Chu, Andrew H.J. Wang

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

The P-loop-containing protein phosphatases are important regulators in signal transduction. These enzymes have structural and functional similarity with a conserved sequence of Dx(25-41) HCsxGxxR(T/S) essential for catalysis. The singular protein tyrosine phosphatase (PTP) from archaeal Sulfolobus solfataricus is one of the smallest known PTPs with extreme thermostability. Here, we report the crystal structure of this phosphatase and its complexes with two tyrosyl phosphopeptides A-(p)Y-R and N-K-(p)Y-G-N. The structure suggests the minimal structural motif of the PTP family, having two variable sequences inserted between the β2-β3 and β3-β4 strands, respectively. The phosphate of both phosphopeptide substrates is bound to the P-loop through several hydrogen bonds. Comparison of several phosphatase-substrate complexes revealed that GM135 on the Q-loop has different modes of recognition toward phosphopeptides. The substrate specificity of SsoPTP is primarily localized at the phosphotyrosine, suggesting that this phosphatase may be a prototypical PTP.

Original languageEnglish
Pages (from-to)996-1003
Number of pages8
JournalProteins: Structure, Function and Genetics
Volume66
Issue number4
DOIs
Publication statusPublished - Mar 2007
Externally publishedYes

Keywords

  • Hyperthermophilic
  • Mutagenesis
  • P-loop
  • Phosphatase
  • Phosphotyrosine
  • Sulfolobus
  • Synchrotron crystallography

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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