Fig. 7: Overlap between postulated and experimentally verified fragment binding sites on p97 with the interaction sites of UFD1. | Communications Chemistry

Fig. 7: Overlap between postulated and experimentally verified fragment binding sites on p97 with the interaction sites of UFD1.

From: Fragment screening using biolayer interferometry reveals ligands targeting the SHP-motif binding site of the AAA+ ATPase p97

Fig. 7

a Binding sites of TROLL7, TROLL8 and TROLL12 identified in the mixed-solvent MD simulations, as well as the crystal structure of TROLL2 superimposed with the bound UFD1-SHP-peptide (PDB entry 5B6C) mapped onto a surface representation of the N-domain. Additionally, the highest chemical shifts of the 1H-15N-HSQC-NMR measurements are shown, colored in terms of standard deviation as in Fig. 6. b Zoom into the SHP II binding site, which is occupied by F228 in the structure of the p97-N-UFD1 peptide complex and is addressed by TROLL2, TROLL7 and TROLL12. Based on the 1H-15N-HSQC-NMR measurements, and, in contrast to the findings from the mixed-solvent MD simulations, TROLL8 seems to bind to a sub-pocket (SHP I) which is occupied by L235 in the structure of the p97-N-UFD1 peptide complex.

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