Structural Stability of Human Protein Tyrosine Phosphatase ρ Catalytic Domain: Effect of Point Mutations
作者： Alessandra Pasquo , Valerio Consalvi , Stefan Knapp , Ivan Alfano , Matteo Ardini
DOI: 10.1371/JOURNAL.PONE.0032555
关键词: Phosphorylation 、 Biochemistry 、 Protein phosphatase 2 、 Protein tyrosine phosphatase 、 Molecular biology 、 Protein structure 、 Amino acid 、 Nonsynonymous substitution 、 Phosphatase 、 Tyrosine 、 Biology
摘要: Protein tyrosine phosphatase ρ (PTPρ) belongs to the classical receptor type IIB family of protein phosphatase, most frequently mutated in human cancer. There are evidences suggest that PTPρ may act as a tumor suppressor gene and dysregulation Tyr phosphorylation can be observed diverse diseases, such diabetes, immune deficiencies variants catalytic domain have been identified cancer tissues. These natural nonsynonymous single nucleotide polymorphisms, variations occurring coding region leading amino acid substitutions. In this study we investigated effect substitution on structural stability activity membrane-proximal PTPρ. We expressed purified soluble recombinant proteins some mutants colorectal polymorphisms database. The show decreased thermal thermodynamic activation energy relative activity, when compared wild- type. All three-state equilibrium unfolding transitions similar type, with accumulation folding intermediate populated at ~4.0 M urea.
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