Representations
of the protein surface for binary and ternary complexes
of hlGPDH: (A) binary complex with NAD (PDB entry 6E8Z), (B) binary complex
with NAD with substrate DHAP inserted at the position observed for
the ternary hlGPDH·NAD·DHAP complex, and
(C) ternary hlGPDH·NAD·DHAP complex (PDB
entry 6E90).
Color key: NAD, cyan; flexible protein loop (292-LNGQKL-297), navy
blue; Q295, olive; R269, red; K120, magenta; DHAP, dark green for
the phosphodianion and khaki for the remainder of the substrate. Substrate
binding is accompanied by a movement of the navy blue flexible protein
loop that covers the substrate and cofactor in the closed enzyme,
formation of a hydrogen bond between the Q295 (olive) and R269 (red)
side chains, and movement of the R269 side chain toward the substrate
phosphodianion (green) and the cofactor pyrophosphate (cyan). The
buried K120 side chain and substrate phosphodianion are hidden from
view in panel C.