G6PD: Molecular biology

The G6PD gene consists of 13 exons and 12 introns which are spread over a region of >100kb on the X chromosome.  Therefore G6PD deficiency is an X-linked genetic defect in which most sufferers of the disease are male. G6PD deficiency is also thought to have a link with malaria in many studies.

G6PD (EC code 1.1.1.49) is the first enzyme of the pentose phosphate pathway, converting alpha-D-glucose-6-phospate from Glycolysis into D-Glucono-1,5-lactone-6-phosphate, and is also involved in Glutathione metabolism

The monomer of human G6PD consists of 514 amino acids and is of molecular weight 59kDa. The active human enzyme exists in an equilibrium between dimer and tetramer, which is affected by pH and ionic strength. Recent determination of the first 3-dimensional crystal structure of human G6PD demonstrates clearly the importance of a structural NADP+ bound to each of the monomeric enzyme molecules for protein stability and provides new insights into the mechanisms of G6PD deficiency. The enzyme structure has two domains, usually termed 'the NADP binding domain' and the 'large domain'. The active site is located between the two domains. The NADP binding domain adopts a Rossman fold whereas the large domain has an alpha-beta fold (see CATH).