Fig. 3: Co-factor binding site and a blocked putative substrate site in apo HSD17B13 structure.

a The cofactor binding site of HSD17B13 selects for NAD⁺(NADH). HSD17B13 residues making hydrogen bonds (dashes) with bound NAD⁺ (stick model with carbon atoms colored magenta) were shown in sticks (green C atoms). As a comparison, the key residues that select for NADP in HSD17B1 (PDB ID 1QYV) were shown with gray C atoms. The putative catalytic triad of HSD17B13 S172, Y185, and K189 are shown and labeled. The substrate-binding loop, P218-T239, was labeled. b The C-terminal peptide of HSD17B13 occupied the putative substrate-binding site. Residues in the C-terminal peptide interacting with the P218-T239 loop were shown in sticks, and hydrogen bonds were shown in dashes. The putative substrate-binding site was indicated with an androstenedione molecule (spheres with C colored gray) docked from HSD17B1 complex structure (PDB ID 1QYX). c zoomed-in view of the electron densities (2Fo-Fc contoured at 1.2σ) surrounding the C-terminal peptide blocking the substrate site.