Chemical activation of divergent protein tyrosine phosphatase domains with cyanine-based biarsenicals.

ABSTRACT: Strategies for the direct chemical activation of specific signaling proteins could provide powerful tools for interrogating cellular signal transduction. However, targeted protein activation is chemically challenging, and few broadly applicable activation strategies for signaling enzymes have been developed. Here we report that classical protein tyrosine phosphatase (PTP) domains from multiple subfamilies can be systematically sensitized to target-specific activation by the cyanine-based biarsenical compounds AsCy3 and AsCy5. Engineering of the activatable PTPs (actPTPs) is achieved by the introduction of three cysteine residues within a conserved loop of the PTP domain, and the positions of the sensitizing mutations are readily identifiable from primary sequence alignments. In the current

SUBMITTER: Plaman BA 

PROVIDER: S-EPMC6834593 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature