Solution structure of the MAPK phosphatase PAC-1 catalytic domain: Insights into substrate-induced enzymatic activation of MKP

Amjad Farooq, Olga Plotnikova, Gaurav Chaturvedi, Sherry Yan, Lei Zeng, Qiang Zhang, Ming Ming Zhou

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Inactivation of mitogen-activated protein kinases (MAPKs) by MAPK phosphatases (MKPs) is accomplished via substrate-induced activation of the latter enzymes; however, the structural basis for the underlying mechanism remains elusive. Here, we report the three-dimensional solution structure of the C-terminal phosphatase domain of the prototypical MKP PAC-1, determined when bound to phosphate. Structural and biochemical analyses reveal unique active site geometry of the enzyme important for binding to phosphorylated threonine and tyrosine of MAPK ERK2. Our study further demonstrates that the dynamic interaction between the N-terminal kinase binding domain and the C-terminal phosphatase domain of an MKP is directly coupled to MAPK-induced conformational change of the phosphatase active site, which is essential for eliciting its full enzymatic activity.

Original languageEnglish
Pages (from-to)155-164
Number of pages10
JournalStructure
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

Fingerprint

Mitogen-Activated Protein Kinase Phosphatases
Mitogen-Activated Protein Kinases
Phosphoric Monoester Hydrolases
Catalytic Domain
Enzyme Activation
Threonine
Tyrosine
Phosphotransferases
Phosphates
Enzymes
2-carboxyarabinitol 1-phosphate

Keywords

  • Enzymatic activation
  • MAPK dephosphorylation
  • MKP phosphatase domain
  • NMR structure
  • PAC-1

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Solution structure of the MAPK phosphatase PAC-1 catalytic domain : Insights into substrate-induced enzymatic activation of MKP. / Farooq, Amjad; Plotnikova, Olga; Chaturvedi, Gaurav; Yan, Sherry; Zeng, Lei; Zhang, Qiang; Zhou, Ming Ming.

In: Structure, Vol. 11, No. 2, 01.02.2003, p. 155-164.

Research output: Contribution to journalArticle

Farooq, Amjad ; Plotnikova, Olga ; Chaturvedi, Gaurav ; Yan, Sherry ; Zeng, Lei ; Zhang, Qiang ; Zhou, Ming Ming. / Solution structure of the MAPK phosphatase PAC-1 catalytic domain : Insights into substrate-induced enzymatic activation of MKP. In: Structure. 2003 ; Vol. 11, No. 2. pp. 155-164.
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