the presence of calcium. Lipocortin III crystals, be- 
longing to the rhombohedral space group R3 with 
cell constants a = 121.3 A and c = 83.0 A (hexago- 
nal setting), diffract beyond 2.5 A resolution. It is 
expected that the determination of these structures 
will reveal a novel calcium-binding motif; future 
structural studies of these proteins in the presence 
and absence of calcium and phospholipid compo- 
nents should elucidate the mechanism of cooper- 
ativity between phospholipid and calcium binding. 
III. Allosteric Regulation of Glycogen 
Phosphorylase. 
The laboratory continues its exploration of the 
structural mechanism of homotropic and hetero- 
tropic cooperativity in this en2ymatic regulator of 
glycogen metabolism. Previous studies, in collabo- 
ration with Dr. Elizabeth Goldsmith (University of 
Texas Southwestern Medical Center at Dallas) and 
Dr. Robert Fletterick (University of California at San 
Francisco), have elucidated the structural basis for 
phosphoregulation and the nature of the structural 
changes that accompany cooperative substrate 
binding. Recent work has focused on the descrip- 
tion of the conformational changes caused by the 
simultaneous presence of substrate and two acti- 
vators, adenosine monophosphate and oligosac- 
charides. This work has shown that the crystalline 
enzyme is able to catalyze the degradation of oligo- 
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saccharides to glucose-l-phosphate, leaving a prod- 
uct complex bound to the active site. The extensive 
conformational changes that result from this reac- 
tion are presently being analyzed. Crystallographic 
studies are also in progress to identify the binding 
site of divalent and trivalent ions, including magne- 
sium and calcium, both of which promote phos- 
phorylase activation. 
IV Structural Studies of G Regulatory Proteins. 
Efficient Escherichia coli expression systems 
have been successfully exploited by Dr. Alfred Gil- 
man (University of Texas Southwestern Medical 
Center at Dallas) to yield milligram quantities of 
the (J-adrenergic receptor-responsive G protein reg- 
ulator of adenylate cyclase, Gsa. In collaboration 
with Dr. Gilman's laboratory, crystallization trials 
(in the presence of nonhydrolyzable guanosine tri- 
phosphate analogues) of Gsa and active tryptic 
fragments of Gsa are now under way. The three-di- 
mensional structures of these molecules should 
contribute to the understanding of the intricate 
mechanism of transmembrane signal transduction 
utilized by this ubiquitous family of regulatory pro- 
teins. 
Dr. Sprang is also Assistant Professor of Biochem- 
istry at the University of Texas Southwestern Medi- 
cal Center at Dallas. 
Articles 
Goldsmith, E.J., Sprang, S.R., Hamlin, R., Xuong, N.-H., and Fletterick, R.J. 1989. Domain separation in the 
activation of glycogen phosphorylase a. Science 245:528-532. 
Sprang, S.R. , Acharya, K.R., Goldsmith, E.J., Stuan, D.I., Varvill, K., Fletterick, R.J., Madsen, N.B., and John- 
son, L.N. 1988. Structural changes in glycogen phosphorylase induced by phosphorylation. Nature 
336:215-221. 
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