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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.

SUBMITTER: Lountos GT

PROVIDER: S-EPMC4321476 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Structural analysis of human dual-specificity phosphatase 22 complexed with a phosphotyrosine-like substrate.

Lountos George T GT Cherry Scott S Tropea Joseph E JE Waugh David S DS

Acta crystallographica. Section F, Structural biology communications 20150128 Pt 2

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 ...[more]

PMID: 25664796

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