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

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 phosphorylat...

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Autores principales:	Alessandra Pasquo, Valerio Consalvi, Stefan Knapp, Ivan Alfano, Matteo Ardini, Simonetta Stefanini, Roberta Chiaraluce
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/27a90974e2a5431eb9108c94ab006e39
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spelling	oai:doaj.org-article:27a90974e2a5431eb9108c94ab006e392021-11-18T07:26:32ZStructural stability of human protein tyrosine phosphatase ρ catalytic domain: effect of point mutations.1932-620310.1371/journal.pone.0032555https://doaj.org/article/27a90974e2a5431eb9108c94ab006e392012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22389709/?tool=EBIhttps://doaj.org/toc/1932-6203Protein 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.Alessandra PasquoValerio ConsalviStefan KnappIvan AlfanoMatteo ArdiniSimonetta StefaniniRoberta ChiaralucePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e32555 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alessandra Pasquo Valerio Consalvi Stefan Knapp Ivan Alfano Matteo Ardini Simonetta Stefanini Roberta Chiaraluce Structural stability of human protein tyrosine phosphatase ρ catalytic domain: effect of point mutations.
description	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.
format	article
author	Alessandra Pasquo Valerio Consalvi Stefan Knapp Ivan Alfano Matteo Ardini Simonetta Stefanini Roberta Chiaraluce
author_facet	Alessandra Pasquo Valerio Consalvi Stefan Knapp Ivan Alfano Matteo Ardini Simonetta Stefanini Roberta Chiaraluce
author_sort	Alessandra Pasquo
title	Structural stability of human protein tyrosine phosphatase ρ catalytic domain: effect of point mutations.
title_short	Structural stability of human protein tyrosine phosphatase ρ catalytic domain: effect of point mutations.
title_full	Structural stability of human protein tyrosine phosphatase ρ catalytic domain: effect of point mutations.
title_fullStr	Structural stability of human protein tyrosine phosphatase ρ catalytic domain: effect of point mutations.
title_full_unstemmed	Structural stability of human protein tyrosine phosphatase ρ catalytic domain: effect of point mutations.
title_sort	structural stability of human protein tyrosine phosphatase ρ catalytic domain: effect of point mutations.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/27a90974e2a5431eb9108c94ab006e39
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_version_	1718423463579877376

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

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