Abelson kinase domain - Complex with Imatinib (Gleevec-tm)
The PYMOL scripts in this section
illustrate the complex of Abl with Gleevec.
Install Pymol - an open source
graphics program by Warren Delano.
The instructions below work on a PC running Windows. Mac users: You'll probably
have to run this
from a Unix window under OSX.
To start the demo, click on the
file named start.pml in the folder.
start.pml shows a rotating view
of the kinase domain of Abl complexed with Gleevec (red). The visualization
alternates between a representation of the protein surface, and a view showing
the polypeptide backbone
of the protein. Notice how Gleevec penetrates the protein structure, from one
side to the other. This work was done in collaboration with the groups of Bayard
Clarkson and William Bornmann at Sloan Kettering Cancer Center, New York.
To run the next demo, type @run1.pml
in the window, at the PYMO> prompt. This shows the sites of resistance
mutations in the Abl kinase domain (pink spheres), in a rotating view of the
kinase domain of Abl. These sites were mapped by Charles
Sawyers and his group at UCLA (see reference at the bottom of the page).
Protein Databank Coordinates
The following coordinates from the protein databank were used to create these
demos. They are included in the downloadable zip file.
Abl Kinase Domain,
complexed with STI-571 (Gleevec, Imatinib): 1IEP.
Reference:
Nagar, B., Bornmann, W. G.,
Pellicena, P., Schindler, T., Veach, D. R., Miller, W. T., Clarkson, B., and
Kuriyan, J. (2002). Crystal Structures of the Kinase Domain of c-Abl in Complex
with the Small Molecule Inhibitors PD173955 and Imatinib (STI-571). Cancer Res
62, 4236-4243.
Shah, N. P., Nicoll, J. M.,
Nagar, B., Gorre, M. E., Paquette, R. L., Kuriyan, J., and Sawyers, C. L. (2002).
Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the
tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis
chronic myeloid leukemia. Cancer Cell 2, 117-125.