CRYSTAL-STRUCTURE AND REACTION-MECHANISM OF 7,8-DIHYDRONEOPTERIN ALDOLASE FROM STAPHYLOCOCCUS-AUREUS

Dihydroneopterin aldolase catalyzes the conversion of 7,8-dihydroneopt erin to 6-hydroxymethyl-7,8-dihydropterin during the de novo synthesis of folic acid from guanosine triphosphate. The gene encoding the dihy droneopterin aldolase from S. aureus has been cloned, sequenced and ex pressed in Escherichia coli. The protein has been purified for biochem ical characterization and its X-ray structure determined at 1.65 Angst rom resolution. The protein forms an octamer of 110,000 M-r molecular weight. Four molecules assemble into a ring, and two rings come togeth er to give a cylinder with a hole of at least 13 Angstrom diameter. Th e structure of the binary complex with the product 6-hydroxymethyl-7,8 -dihydropterin has defined the location of the active site. The struct ural information and results of site directed mutagenesis allow an enz yme reaction mechanism to be proposed.