Fig. 6: Autoinhibited structure of PLK1 generated using AlphaFold [93].
From: Structural regulation of PLK1 activity: implications for cell cycle function and drug discovery
The structure generated was found to be in the autoinhibited, closed conformation state, and shows the IDL (purple) bridging the KD and PBD, a key detail absent in the Danio structure [69]. The kinase domain represents the overlay of the co-crystal structure of the isolated KD structure bound to BI2536. The two polo boxes of the PBD are shown in ribbon form. When the KD inhibitor BI2536 (lavender surface) was modeled into the active site, a severe steric clash occurs with Pro403 of the PB1 of the PBD. Experimental data strongly suggests that this results in an open but catalytically inactive conformation of PLK1.
