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. Author manuscript; available in PMC: 2020 Mar 21.
Published in final edited form as: Cell Chem Biol. 2019 Jan 3;26(3):390–399.e5. doi: 10.1016/j.chembiol.2018.11.005

Figure 4: Structural hallmarks of DDR1 and other promiscuous kinases.

Figure 4:

A) Sequence alignment of the eight promiscuous kinases around Thr664 (the ‘gatekeeper’ mutant), Asp671, and Arg752 (DDR1 numbering). Dark blue highlights residues enriched in the promiscuous set by 50% or more and cyan indicates residues enriched by 10–50% according to Two Sequence Logo comparison (using p-value cutoff 0.01) of the promiscuous kinases to the other 483 kinases analyzed. Bottom: All residues enriched in our promiscuous set by 50% or more are shown as blue surface on the DDR1-VX680 structure. B) Potential salt bridges between residues equivalent to DDR1 Asp671 and Arg752 are shown for representative structures: CSF1R (PDB IDs: 3KRL and 2IOV) in pale cyan, c-Kit (PDB IDs: IT45 and IT46) in pink, DDR1 (PDB IDs: 5FDP and 5BVO) in orange, and PDGFRA (PDB ID: 5GRN) in teal. C) The structures of VX-680 bound to DDR1 (top) and Abl (bottom, PDB entry 2F4J) illustrate the hydrophobic shield formed by the activation loop (blue) and the P-loop (red), respectively. See also Figure S5.