FIGURE 5.

Cofactor specificity of RDH10. A, ribbon representation of the dehydrogenase domain of human 17β-HSD4 (PDB code 1ZBQ). Shown is the view of the cofactor binding region of the Rossmann fold with bound NAD⁺. NAD⁺ and D40 are shown as stick models (CPK, carbon gray and CPK, carbon yellow, respectively). Hydrogen bonds between Asp-40 and NAD⁺ are shown in yellow. Molecular graphics for structural representation were made using PyMol (DeLano Scientific LLC, Palo Alto, CA). B, structural alignment of NAD⁺-dependent SDRs. The secondary structure elements are indicated as arrows for β-strands and as cylinders for α-helices. Conserved aspartate residues that determine the preference for NAD⁺ are highlighted in yellow. Gly residues that constitute the GXXXGXG cofactor-binding motif are shown in dark pink. 1GEG, crystal structure of meso-2,3-butanediol dehydrogenase in a complex with NAD⁺ and inhibitor mercaptoethanol; 2GDZ, crystal structure of 15-hydroxyprostaglandin dehydrogenase type 1, complexed with NAD⁺.