Structural stability of human protein tyrosine phosphatase ρ catalytic domain: Effect of point mutations

Alessandra Pasquo, Valerio Consalvi, Stefan Knapp, Ivan Alfano, Matteo Ardini, Simonetta Stefanini, Roberta Chiaraluce

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8 Citations (Scopus)

Abstract

Protein tyrosine phosphatase ρ (PTPρ) belongs to the classical receptor type IIB family of protein tyrosine phosphatase, the most frequently mutated tyrosine phosphatase in human cancer. There are evidences to suggest that PTPρ may act as a tumor suppressor gene and dysregulation of Tyr phosphorylation can be observed in diverse diseases, such as diabetes, immune deficiencies and cancer. PTPρ variants in the catalytic domain have been identified in cancer tissues. These natural variants are nonsynonymous single nucleotide polymorphisms, variations of a single nucleotide occurring in the coding region and leading to amino acid substitutions. In this study we investigated the effect of amino acid substitution on the structural stability and on the activity of the membrane-proximal catalytic domain of PTPρ. We expressed and purified as soluble recombinant proteins some of the mutants of the membrane-proximal catalytic domain of PTPρ identified in colorectal cancer and in the single nucleotide polymorphisms database. The mutants show a decreased thermal and thermodynamic stability and decreased activation energy relative to phosphatase activity, when compared to wild- type. All the variants show three-state equilibrium unfolding transitions similar to that of the wild- type, with the accumulation of a folding intermediate populated at ~4.0 M urea. © 2012 Pasquo et al.
Original languageEnglish
Article numbere32555
Pages (from-to)-
JournalPLoS One
Volume7
Issue number2
DOIs
Publication statusPublished - 28 Feb 2012
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Pasquo, A., Consalvi, V., Knapp, S., Alfano, I., Ardini, M., Stefanini, S., & Chiaraluce, R. (2012). Structural stability of human protein tyrosine phosphatase ρ catalytic domain: Effect of point mutations. PLoS One, 7(2), -. [e32555]. https://doi.org/10.1371/journal.pone.0032555