Fig. 4: The structure of human wild-type MECR and the MECR G165Q variant.

Crystal structure of the (a) wild-type MECR of this study (PDB entry 7AYB), and (b) the MECR G165Q mutant (PDB entry 7AYC). Only one monomer of the dimeric MECR is shown. The catalytic domain is colored pale cyan and the cofactor binding domain is colored light pink. The mutation site is highlighted. NH2 and COOH label the N-terminus and C-terminus. c The structural comparison of the superposed wild-type MECR and MECR G165Q variant. The stereo diagram showing the conformational changes in MECR G165Q variant structure due to the mutation. Residues of wild-type protein are shown in light blue color and the residues of mutant protein are labeled in magenta color. The side chain of the selected residues are shown in stick representation with N and O atoms colored blue and red, respectively. It can be noted that the (phi/psi) values of G165 in wild-type would allow for the mutation into a residue with a side chain: (phi/psi) G165 (wild-type) = −73/−11; (phi/psi) Q165 (G165Q) = −84/−55. d Detailed view of the fatty acyl binding cavity of wild-type MECR with a modeled C16-substrate. The cavity for fatty acyl tail is shown as “cavity surface” option (light gray + transparent) and the bottom of the cavity is shown with red arrow. e Fatty acyl binding cavity in the G165Q structure is shown as “cavity surface” option (light gray + transparent) and the bottom of the cavity is shown with red arrow. Hydrogen-bonding network is changed significantly and the loop region containing A133 and N132 moves slightly as also seen in the panel c.