Publications

BibTex format

@article{Gilburt:2017:10.1002/ange.201704654,
author = {Gilburt, JAH and Sarkar, H and Sheldrake, P and Blagg, J and Ying, L and Dodson, CA},
doi = {10.1002/ange.201704654},
journal = {Angewandte Chemie},
pages = {11567--11572},
title = {Dynamic Equilibrium of the Aurora A Kinase Activation Loop Revealed by Single-Molecule Spectroscopy},
url = {http://dx.doi.org/10.1002/ange.201704654},
volume = {129},
year = {2017}
}

Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The conformation of the activation loop (T-loop) of protein kinases underlies enzymatic activity and influences the binding of small-molecule inhibitors. By using single-molecule fluorescence spectroscopy, we have determined that phosphorylated AuroraA kinase is in dynamic equilibrium between a DFG-in-like active T-loop conformation and a DFG-out-like inactive conformation, and have measured the rate constants of interconversion. Addition of the AuroraA activating protein TPX2 shifts the equilibrium towards an active T-loop conformation whereas addition of the inhibitors MLN8054 and CD532 favors an inactive T-loop. We show that AuroraA binds TPX2 and MLN8054 simultaneously and provide a new model for kinase conformational behavior. Our approach will enable conformation-specific effects to be integrated into inhibitor discovery across the kinome, and we outline some immediate consequences for structure-based drug discovery.
AU  - Gilburt,JAH
AU  - Sarkar,H
AU  - Sheldrake,P
AU  - Blagg,J
AU  - Ying,L
AU  - Dodson,CA
DO  - 10.1002/ange.201704654
EP  - 11572
PY  - 2017///
SN  - 0044-8249
SP  - 11567
TI  - Dynamic Equilibrium of the Aurora A Kinase Activation Loop Revealed by Single-Molecule Spectroscopy
T2  - Angewandte Chemie
UR  - http://dx.doi.org/10.1002/ange.201704654
UR  - http://hdl.handle.net/10044/1/49334
VL  - 129
ER  -

Download

DrLimingYing

Contact

Location

Summary

Citation

BibTex format

RIS format (EndNote, RefMan)