Structural and kinetic characterization of DUSP5 with a Di-phosphorylated tripeptide substrate from the ERK activation loop.

ABSTRACT:

Introduction

Dual specific phosphatases (DUSPs) are mitogen-activated protein kinase (MAPK) regulators, which also serve as drug targets for treating various vascular diseases. Previously, we have presented mechanistic characterizations of DUSP5 and its interaction with pERK, proposing a dual active site.

Methods

Herein, we characterize the interactions between the DUSP5 phosphatase domain and the pT-E-pY activation loop of ERK2, with specific active site assignments. We also report the full NMR chemical shift assignments of DUSP5 that now enable chemical shift perturbation and dynamics studies.

Results and discussion

Both phosphates of the pT-E-pY tripeptide are dephosphorylated, based on ³¹P NMR; but, steady state kinetic studies of the tripeptide both as

SUBMITTER: Imhoff A 

PROVIDER: S-EPMC11694514 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature