Isocitrate dehydrogenase is a catabolic enzyme that acts during the third step
of the tricarboxylic acid cycle. The hypothetical protein ST2166 from the
archaeon Sulfolobus tokodaii was isolated and crystallized. It shares
high primary structure homology with prokaryotic NADP+-dependent
IDHs, suggesting that these enzymes share a common enzymatic mechanism. The
crystal structure of ST2166 was determined at 2.0 Å resolution in the apo
form, and then the structure of the crystal soaked with NADP+ was
also determined at 2.4 Å resolution, which contained NADP+ bound
at the putative active site. Comparisons between the structures of apo and
NADP+-bound forms and NADP-IDHs from other prokaryotes suggest that
prokaryotic NADP-IDHs recognize their cofactors using conserved Lys335, Tyr336,
and Arg386 in ST2166 at the opening cleft before the domain closure.