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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22389709/?tool=EBI |
| _version_ | 1828897606901694464 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T15:00:42Z |
| format | Article |
| id | doaj.art-27a90974e2a5431eb9108c94ab006e39 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T15:00:42Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-27a90974e2a5431eb9108c94ab006e392022-12-21T23:41:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0172e3255510.1371/journal.pone.0032555Structural stability of human protein tyrosine phosphatase ρ catalytic domain: effect of point mutations.Alessandra PasquoValerio ConsalviStefan KnappIvan AlfanoMatteo ArdiniSimonetta StefaniniRoberta ChiaraluceProtein 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22389709/?tool=EBI |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22389709/?tool=EBI |
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