Gleevec (Imatinib) is a very effective drug for treating chronic myelogenous leukemia. It acts by binding to and inhibiting the signaling molecule Abl kinase with extreme specificity. Abl kinase is very closely related to Src kinase, and, in fact, the drug binding pocket for Gleevec is almost identical between the two proteins. Interestingly, however, Gleevec binds to Abl 3000 fold more tightly than it does to Src. Why? In her second talk, Kern answers this question. Her lab used NMR, and the techniques she described in Part 1, to show that the protein dynamics of Abl and Src are dramatically different when Gleevec is bound. In a clever experiment in which they synthesized proteins that were likely evolutionary ancestors of Src and Abl, Kern’s lab was able to show how changes in amino acids throughout the kinases determined the differential binding affinity of Gleevec for Abl kinase over Src kinase. Experiments such as these demonstrate the importance of understanding protein dynamics at the atomic level of the whole protein, not just the drug binding site, when designing new drugs.
View the full talk with additional resources on our website
Visualizing Protein Dynamics
Dorothee Kern explains how visualizing protein dynamics (i.e. watching proteins in action) allows us to better understand protein function and optimize drug design. (Talk recorded in July 2017)
- Part 1: Visualizing Protein DynamicsAudience:
- Student
- Researcher
- Educators of H. School / Intro Undergrad
- Educators of Adv. Undergrad / Grad
Duration: 38:33 - Part 2: Using Evolution to Reveal a Cancer Drug’s MechanismAudience:
- Researcher
- Educators of Adv. Undergrad / Grad
Duration: 29:51