Issues

X-ray crystal structures of flavonoids bound to the ATP-binding site of the PIM1 kinase. Two distinct orientations were observed. Quercetagetin orients the B ring inside the pocket (orientation I), whereas both myricetin and 5,7,3′,4′,5′-pentahydroxyflavone flip the B ring out toward solvent (orientation II). Both binding orientations have been observed in the crystal structures of flavonoids bound to other kinases. Quercetin in complex with phosphatidylinositol 3-kinase γ (1E8W) and fisetin in complex with cyclin-dependent kinase 6 (1XO2) represent orientation I, whereas quercetin in complex with hematopoetic cell kinase (2HCK) exemplifies orientation II. For details, see Holder et al. in this issue.