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    PP1:Tautomycetin Complex Reveals a Path toward the Development of PP1-Specific Inhibitors. Choy Meng S,Swingle Mark,D'Arcy Brandon,Abney Kevin,Rusin Scott F,Kettenbach Arminja N,Page Rebecca,Honkanen Richard E,Peti Wolfgang Journal of the American Chemical Society Selective inhibitors for each serine/threonine phosphatase (PPP) are essential to investigate the biological actions of PPPs and to guide drug development. Biologically diverse organisms (e.g., cyanobacteria, dinoflagellates, beetles) produce structurally distinct toxins that are catalytic inhibitors of PPPs. However, most toxins exhibit little selectivity, typically inhibiting multiple family members with similar potencies. Thus, the use of these toxins as chemical tools to study the relationship between individual PPPs and their biological substrates, and how disruptions in these relationships contributes to human disease, is severely limited. Here, we show that tautomycetin (TTN) is highly selective for a single PPP, protein phosphatase 1 (PP1/PPP1C). Our structure of the PP1:TTN complex reveals that PP1 selectivity is defined by a covalent bond between TTN and a PP1-specific cysteine residue, Cys127. Together, these data provide key molecular insights needed for the development of novel probes targeting single PPPs, especially PP1. 10.1021/jacs.7b09368
    Targeting phosphatases in cancer: suppression of many versus the ablation of one. D'Arcy Brandon M,Prakash Aishwarya,Honkanen Richard E Oncotarget 10.18632/oncotarget.27201