Dynamics in the p38 MAP Kinase-SB203580 Complex Observed by Liquid-State NMR Spectroscopy

摘要

Diaryl-heterocycle compounds were the first small-molecule inhibitors targeting mitogen-activated protein (MAP) kinases.[1] The diaryl heterocycle SB203580 binds in an adenosine triphosphate (ATP) competitive manner to inactive and active p38 MAP kinase with similar IC50 values.[2] A dissociation constant (KD) of 11.5 nM was reported for the inactive form.[3] Crystallographic studies showed that SB203580 binds in the ATP-binding site of p38. Similarly to ATP, the pyridine nitrogen atom of SB203580 forms a hydrogen bond to the backbone amide of Met109 from the hinge region.