Glucose-6-phosphate dehydrogenase is the first enzyme in the pentose phosphate
pathway. The reaction catalyzed by the enzyme is considered to be the main
source of reducing power for nicotinamide adenine dinucleotide phosphate (NADPH)
and is a precursor of 5-carbon sugar used by cells. To uncover the structural
features of the enzyme, we determined the crystal structures of
glucose-6-phosphate dehydrogenase from Kluyveromyces lactis (KlG6PD) in both the
apo form and a binary complex with its substrate glucose-6-phosphate. KlG6PD
contains a Rossman-like domain for cofactor NADPH binding; it also presents a
typical antiparallel β sheet at the C-terminal domain with relatively the same
pattern as those of other homologous structures. Moreover, our structural and
biochemical analyses revealed that Lys153 contributes significantly to substrate
G6P recognition. This study may provide insights into the structural variation
and catalytic features of the G6PD enzyme.
