Solution of the structure of tetrameric human glucose 6-phosphate dehydrogenase by molecular replacement

Recombinant human glucose 6-phosphate dehydrogenase (G6PD) has been crystallized and its structure solved by molecular replacement, Crystals of the natural mutant R459L grow under similar conditions in space groups P2(1)2(1)2(1) and C222(1) with eight or four 515-residue molecules in the asymmetric unit, respectively. A non-crystallographic 222 tetramer was found in the C222(1) crystal form using a 4 Angstrom resolution data set and a dimer of the large beta + alpha domains of the Leuconostoc mesenteroides enzyme as a search model, This tetramer was the only successful search model for the P2(1)2(1)2(1) crystal form using data to 3 Angstrom. Crystals of the deletion mutant Delta G6PD grow in space group F222 with a monomer in the asymmetric unit; 2.5 Angstrom resolution data have been collected. Comparison of the packing of tetramers in the three space groups suggests that the N-terminal tail of the enzyme prevents crystallization with exact 222 molecular symmetry.