SHP-1 Variants Broaden the Understanding of pH-Dependent Activities in Protein Tyrosine Phosphatases.

ABSTRACT: The protein tyrosine phosphatase (PTP) SHP-1 plays an important role in both immune regulation and oncogenesis. This enzyme is part of a broader family of PTPs that all play important regulatory roles in vivo. Common to these enzymes is a highly conserved aspartic acid (D421 in SHP-1) that acts as an acid/base catalyst during the PTP-catalyzed reaction. This residue is located on a mobile loop, the WPD-loop, the dynamic behavior of which is intimately connected to the catalytic activity. The SHP-1 WPD-loop variants H422Q, E427A, and S418A have been kinetically characterized and compared to those of the wild-type (WT) enzyme. These variants exhibit limiting magnitudes of k _cat ranging from 43 to 77% of the WT enzyme. However, their pH profiles are significantly broadened i

SUBMITTER: Shen R 

PROVIDER: S-EPMC11350601 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature