Conformational selection vs. induced fit: insights into the binding mechanisms of p38α MAP Kinase inhibitors
The conformational dynamics of a kinase's activation loop have been challenging to assess due to the activation loop's intrinsic flexibility. To directly probe the conformational equilibrium of the activation loop of mitogen-activated protein kinase p38α, we present an approach based on si...
Saved in:
Published in | Chemical communications (Cambridge, England) Vol. 56; no. 62; pp. 8818 - 8821 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
England
Royal Society of Chemistry
04.08.2020
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | The conformational dynamics of a kinase's activation loop have been challenging to assess due to the activation loop's intrinsic flexibility. To directly probe the conformational equilibrium of the activation loop of mitogen-activated protein kinase p38α, we present an approach based on site-directed spin labeling, electron paramagnetic resonance (EPR) distance restraints, and multilateration. We demonstrate that the activation loop of apo p38α resides in a highly flexible equilibrium state and we reveal that binding of small molecules significantly alters this equilibrium and the populated sub-states. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1359-7345 1364-548X |
DOI: | 10.1039/d0cc02539a |