1H, 15N, 13C resonance assignments of the reduced and active form of human Protein Tyrosine Phosphatase, PRL-1.
Phosphatase of regenerating liver-1 (PRL-1) is a novel target for potentially treating cancer metastases. Although its specific biochemical role in these processes has yet to be delineated, considerable evidence suggests the phosphatase activity of PRL-1 is required for promoting cancer and metastasis. PRL-1 belongs to the protein tyrosine phosphatase (PTPase) family and functions using the CX(5)R consensus active site motif. Like other PTPases, PRL-1 is inhibited by oxidation at its active site Cys, however, disulfide bond formation occurs unusually readily in wild-type PRL-1. Chemical shift assignments are available for oxidized wild type, but numerous, substantial changes are observed in the spectra upon reduction. Because the reduced form is active, we sought to identify a stable mutant that would resist oxidation and be useful for facilitating drug screening and development using NMR-based assays. We present here NMR assignments for a full-length, reduced and active form of PRL-1, PRL-1-C170S-C171S, that is well suited for this purpose.
Skinner
Andria L
AL
Department of Pharmaceutical Chemistry, The University of Kansas, Multidisciplinary Research Building Room 356, 2030 Becker Dr, Lawrence, KS 66047, USA.
Laurence
Jennifer S
JS
D000595:Amino Acid Sequence; D002247:Carbon Isotopes / Q000737:chemistry; D018797:Cell Cycle Proteins / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D009587:Nitrogen Isotopes / Q000737:chemistry; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry*; D011522:Protons
D002247:Carbon Isotopes; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D009587:Nitrogen Isotopes; D011522:Protons; C490198:PTP4A1 protein, human; D017027:Protein Tyrosine Phosphatases