• Publications
  • Influence
Expressed protein ligation: a general method for protein engineering.
This work illustrates that expressed protein ligation is a simple and powerful new method in protein engineering to introduce sequences of unnatural amino acids, posttranslational modifications, and biophysical probes into proteins of any size.
Protein Lysine Acetylation by p300/CBP
The current understanding of p300/CBP is summarized including the novel technologies developed for these studies, which revealed that acetyl-CoA binds in a tunnel enclosed by a unique loop, while the substrate protein transiently associates with an acidic patch, following a hit-and-run kinetic mechanism.
The structural basis of protein acetylation by the p300/CBP transcriptional coactivator
A high-resolution X-ray crystal structure of a semi-synthetic heterodimeric p300 HAT domain in complex with a bi-substrate inhibitor, Lys-CoA is described, showing that p300/CBP is a distant cousin of other structurally characterized HATs, but reveals several novel features that explain the broad substrate specificity and preference for nearby basic residues.
Inhibition of the EGF Receptor by Binding to an Activating Kinase Domain Interface
It is shown that signalling by EGFR molecules that contain constitutively active kinase domains still requires formation of the asymmetric dimer, underscoring the importance of dimer interface blockage in MIG6-mediated inhibition.
Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours
The results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.