title: Structural analysis of human dual-specificity phosphatase 22 complexed with a phosphotyrosine-like substrate.
abstract: 4-Nitrophenyl phosphate (p-nitrophenyl phosphate, pNPP) is widely used as a small molecule phosphotyrosine-like substrate in activity assays for protein tyrosine phosphatases. It is a colorless substrate that upon hydrolysis is converted to a yellow 4-nitrophenolate ion that can be monitored by absorbance at 405 nm. Therefore, the pNPP assay has been widely adopted as a quick and simple method to assess phosphatase activity and is also commonly used in assays to screen for inhibitors. Here, the first crystal structure is presented of a dual-specificity phosphatase, human dual-specificity phosphatase 22 (DUSP22), in complex with pNPP. The structure illuminates the molecular basis for substrate binding and may also facilitate the structure-assisted development of DUSP22 inhibitors.
authors: Basic Science Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors: George T
authors: GT
authors: Lountos
authors: Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
authors: Scott
authors: S
authors: Cherry
authors: Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
authors: Joseph E
authors: JE
authors: Tropea
authors: Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
authors: David S
authors: DS
authors: Waugh
mesh_terms: D002021:Buffers; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D054637:Dual-Specificity Phosphatases / Q000737:chemistry*; D006801:Humans; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000737:chemistry*; D008958:Models, Molecular; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D019000:Phosphotyrosine / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013379:Substrate Specificity
chemical_list: D002021:Buffers; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D019000:Phosphotyrosine; C008644:nitrophenylphosphate; D054639:Mitogen-Activated Protein Kinase Phosphatases; C442824:DUSP22 protein, human; D054637:Dual-Specificity Phosphatases
keywords: 4-nitrophenyl phosphate; dual-specificity phosphatase 22