Vaccinia H1-related (VHR) phosphatase is a dual-specific phosphatase (DSPs). VHR is a potential drug target as it is upregulated in cervical and prostate cancer cells. However, the comprehensive study on the substrate specificity of VHR has not been explored. In this work, the substrate specificity of VHR has been determined by using one-bead-one-compound (OBOC) phosphotyrosine peptide libraries. The library screening reveals two distinct types of peptide substrates, which have been confirmed by solution-phase kinetic analysis.  Mutagenesis studies and molecular dynamics simulation have been performed to identify the binding interactions of the selected peptides and VHR. The specificity profile may be useful to predict their physiological substrates in signaling pathways.

Determination of the substrate specificity of dual-specificy phosphatase VHR and discovery of a novel substrate-binding mode

244th National Meeting (2012)

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