<scp>PTP</scp> Inhibitor V Inhibits Dual‐specificity Phosphatase 22 (<scp>DUSP22</scp>) Activity

Seo, Huiyun; Cho, Sayeon

doi:10.1002/bkcs.10444

Cited by 2 publications

(1 citation statement)

References 33 publications

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“…Thus, it is likely that the water-mediated interaction by Q1663 contributes a major force for the inhibitor interaction. To analyze effects of the same mutations in the binding of a competitive inhibitor, we per formed IC 50 measurements by using a competitive inhibitor, PTP inhibitor V (Choun, 2014;Seo and Cho, 2015) (Table 2). In comparison to the Allo1 IC 50 increase by the mutations, the IC 50 of the PTP inhibitor V was not affected by the same mutations, supporting that Allo1 binding site is not related to the catalytic pocket where the competitive inhibitor binds.…”

Section: Mutagenesis Of the Allo1 Binding Sitementioning

confidence: 99%

Structural studies of the complex of PTPσ with an allosteric inhibitor Allo1

Kim

Ryu

2022

BIODESIGN

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Protein tyrosine phosphatases (PTPs) regulate cell signaling pathways implicated in cancers, diabetes, immune diseases, and neurological diseases. Although PTPs are drug targets, inhibitor development has been limited by the low selectivity caused by the shallow PTP active site pocket with a conserved motif. Recent studies on PTP inhibitors have highlighted allosteric inhibition to circumvent these difficulties. PTPσ is a receptor-type PTP with phosphatase activity in the cytoplasmic region. PTPσ plays a critical role in neural development and hematopoietic stem cell regeneration and have been regarded as a drug target. We determined the crystal structure of the PTPσ complexed with its allosteric inhibitor Allo1. The structure showed an inhibitor-binding near the WPD loop, restricting the loop conformation switch during the catalysis. The allosteric binding site was further confirmed through mutagenesis and in vitro enzyme assays. The structural information can be exploited for the development of potent inhibitors.

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Section: Mutagenesis Of the Allo1 Binding Sitementioning

confidence: 99%