subunits were in similar, closed conformations whereas the PE adopted an open

conformation, differing from the other two by a large hinge motion of the carboxyl

terminal domain of greater that 20 A+. Subsequently, several high-resolution structures of

crystals obtained under various nucleotide conditions gave the same overall structure of

bovine Fl with two nucleotides bound ("two nucleotide structures") (44-49). The PTP Site

was found to occasionally contain a diphosphate nucleotide, establishing that there is no

requirement for PTP to be occupied by a nucleotide triphoshate to produce a

conformational change (48). A more recent structure of bovine Fl solved by the Walker

group at 2.0 A+ showed all three catalytic sites bound by nucleotide (50). Both the PTP

and PDP Sites contained MgADP, adopting the closed conformation, whereas the site

corresponding to the PE Site in previous structures contained MgADP+Pi and adopted a

half-closed conformation. It is thought that the PDP Site is actually the catalytic site. The

structure of rat liver Fl was solved (2.8 A+) in the presence of physiological concentrations

of nucleotides but in the absence of the physiological cation, Mg2+. In this structure, all

three nucleotide binding sites adopted strikingly similar conformations, analogous to the

PDP and PTP Of the previously reported structure of the bovine Fl. This structure had no

indication of the open conformation and showed the presence of nucleotide in all three

sites (21). The structure of an OE3s 3COmplex from a thermophilic bacterium was solved

in the absence of nucleotides and exhibited all three P subunits in the open conformation,

suggesting there is a correlation between the open conformation and the absence of

nucleotide (5 1). A low resolution crystal structure (4.4 A+) of the E. coli Fl has been

obtained by Capaldi's group, in which the catalytic sites are thought to be very similar to

that of the bovine structure; however, the occupancy state of the nucleotide binding sites