RETRACTED: An ATP-competitive inhibitor modulates the allosteric function of the HER3 pseudokinase.

ABSTRACT: Human epidermal growth factor receptor 3 (HER3) is a receptor tyrosine kinase that lacks catalytic activity but is essential for cellular homeostasis due to its ability to allosterically activate EGFR and HER2. Although catalytically inactive, HER3 binds ATP tightly, hinting at a possible role of the nucleotide-binding pocket in modulating HER3 function. We report a structure of the HER3 pseudokinase bound to the ATP-competitive inhibitor bosutinib. Previously solved structures show that bosutinib can potently interact with multiple kinase domain conformations. In complex with HER3, bosutinib binds to yet another conformation, which is nearly identical to that observed in the HER3-ATP complex. Interestingly, occupation of the ATP-binding site by bosutinib improves the ability of HER3 to ac

SUBMITTER: Littlefield P 

PROVIDER: S-EPMC4018233 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature