Comparison between imatinib-NQO2 and imatinib-kinase binding modes. A) The structure of imatinib bound to the kinase domain of Abl (PDB ID 1IEP) . Imatinib binds in an extended conformation, with the pyridylpyrimidine moiety (rings A and B) trans to the methylbenzene and benzamide rings (rings C and D). B) The structure of imatinib bound to the kinase domain of Syk (PDB ID 1XBB) . Imatinib binds in a compact conformation, with the pyridylpyrimidine moiety cis to the methylbenzene and benzamide rings. C) The conformation of imatinib bound to NQO2 most resembles the cis kinase-binding conformation. Shown are the structures of imatinib from the Syk complex 1XBB (yellow), the Abl complex (green), and the NQO2 complex (blue), with their pyridylpyrimidine moieties superimposed. In all panels, proteins are shown in ribbon representation and imatinib is shown as a stick model. The imatinib rings are lettered as in Figure 1A.
Winger et al. BMC Structural Biology 2009 9:7 doi:10.1186/1472-6807-9-7