Fig. 5: Structure of human mutant HSD17B13/compound 2 complex.

a Conformational changes of HSD17B13 caused by compound 2 (light blue C atoms, stick model) binding. Lipids/detergent molecules are also observed in the ligand binding site (orange carbon, stick model). For clarity, only the ligand binding site and the membrane anchoring domain from one subunit are shown. The complex structure was superimposed with the apo dog HSD17B13 structure (gray ribbons). Key residues are labeled. b Detailed interactions of compound 2 with HSD17B13. Residues that contacted compound 2 are labeled. Hydrogen bonds are in dashes. c Comparison of binding modes of compound 2 and compound 1 (cyan C atoms) at the ligand binding site of human HSD17B13/compound 2 complex (gray surface). The area of HSD17B13 with which the F-phenyl group of compound 1 clashes is from the extended helix, P274-A291. d To show the model quality, compound 2 was shown embedded in the initial 2Fo-Fc electron density map calculated before the ligand was included.