Inadverent activation of Abelson Tyrosine Kinase (Abl) causes chronic myelogenous leukemia (CML). This leads to overproduction of white cells within the bone marrow which crowds the bone marrow and disrupts normal blood cell production. A small molecule inhibitor (STI-571) is effective in treatment of CML. This model demonstrates the various interactions between residues and the inhibitor including many hydrogen bonds and Van Der Waals interactions. Those interactions improve the stability and enhance the affinity of the binding. The indicated native structure of Abl is also important to the specific binding to STI-571. The binding of STI-571 is the adoption by the kinase of an inactive conformation, in which a centrally located “activation loop” is not phosphorylated.
PDB ID: 1FPU , DOI: 10.1126/science.289.5486.1938 & PMID: 12154025
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