Fig. 3. Structural comparisons of the αβ and αγ heterodimers in the apo β-mutant HsIDH3 and in the isolated forms.

a Comparison of the αγ heterodimer in the heterooctamer of HsIDH3 and in the isolated forms at the heterodimer interface. The color coding of the subunits and structures is shown above. The key residues at the active site (Tyr126^A2), the allosteric site (Arg97^G, Tyr135^G, and Arg272^G), and the heterodimer interface (Lys151^G and Lys142^A2) assume similar conformations as those in the inactive α^Mgγ structure (PDB code: 5GRH) rather than those in the active α^Mgγ^Mg+CIT+ADP structure (PDB code: 5GRF). b Comparison of the overall conformation of the αβ heterodimer in the heterooctamer of HsIDH3 with that of the isolated α^Caβ heterodimer (PDB code: 6KDE) (in gray, left panel) and α^Mgγ heterodimer (in yellow, right panel). The αβ heterodimer assumes an open overall conformation similar to that of the isolated α^Mgγ heterodimer rather than the compact conformation of the isolated α^Caβ heterodimer. For clarity, only the α helices and β strands are shown, and the loops are omitted except the β12-β8 loops of the β and γ subunits. The N-terminal of the γ subunit from another heterotetramer is also shown. c Comparison of the αβ heterodimer in the heterooctamer of HsIDH3 with the isolated α^Mgγ heterodimer and α^Mgγ^Mg+CIT+ADP heterodimer. The key residues at the active site (Tyr126^A1), the pseudo allosteric site (Arg99^B, Tyr137^B, and Arg274^B), and the heterodimer interface (Lys153^B and Lys142^A1) assume similar conformations as those in the inactive α^Mgγ structure rather than those in the active α^Mgγ^Mg+CIT+ADP structure. d The β12^B-β8^B loop of the β subunit in the heterooctamer of HsIDH3 exhibits some conformational differences from that in the isolated α^Caβ heterodimer but still occupies the ADP-binding site in the α^Mgγ^Mg+CIT+ADP structure. The hydrogen-bonding interactions of the β12^B-β8^B loop with the α7^B and α6^A1 helices are indicated with dashed lines.