Direct monitoring of the conformational equilibria of the activation loop in the mitogen-activated protein kinase p38α

Patrick Roser; Jörn Weisner; Jeffrey R Simard; Daniel Rauh; Malte Drescher

doi:10.1039/c8cc06128a

Direct monitoring of the conformational equilibria of the activation loop in the mitogen-activated protein kinase p38α

Chem Commun (Camb). 2018 Oct 23;54(85):12057-12060. doi: 10.1039/c8cc06128a.

Authors

Patrick Roser¹, Jörn Weisner, Jeffrey R Simard, Daniel Rauh, Malte Drescher

Affiliation

¹ Department of Chemistry and Konstanz Research School Chemical Biology, (KoRS-CB), University of Konstanz, Universitätsstraße 10, 78457 Konstanz, Germany. [email protected].

PMID: 30295691
DOI: 10.1039/c8cc06128a

Abstract

Conformational transitions in protein kinases are crucial for the biological function of these enzymes. Here, we characterize and assess conformational equilibria of the activation loop and the effect of small molecule inhibitors in the MAP kinase p38α. Our work experimentally revealed the existence of a two-state equilibrium for p38α while the addition of inhibitors shifts the equilibrium between these two states.

MeSH terms

Binding Sites
Cyclic N-Oxides / chemistry*
Electron Spin Resonance Spectroscopy
Humans
Kinetics
Ligands
Mesylates / chemistry*
Mitogen-Activated Protein Kinase 14 / chemistry
Mitogen-Activated Protein Kinase 14 / genetics
Mitogen-Activated Protein Kinase 14 / metabolism*
Point Mutation
Protein Conformation
Protein Kinase Inhibitors / chemistry
Spin Labels

Substances

Cyclic N-Oxides
Ligands
Mesylates
Protein Kinase Inhibitors
Spin Labels
(1-oxyl-2,2,5,5-tetramethylpyrroline-3-methyl)methanethiosulfonate
Mitogen-Activated Protein Kinase 14