Chemistry of Cellular Regulation 
pairs, or exactly two helical turns of DNA. Our 
studies (in collaboration with Werner Maas, New 
York University) support the inference that the 
operator must be sharply bent as it wraps around 
the hexamer. In view of the distortion that this 
protein can introduce into DNA, it is interesting 
that the arg repressor has been implicated as a 
-binding "scaffold" in the site-specific recombina- 
tion process that resolves fused ColEl plasmids. 
The architecture of this protein-DNA complex 
should give insight into the DNA topology in- 
volved in site-specific recombination. 
Transmembrane Signaling 
In the area of transmembrane signaling, we 
have recently solved (in collaboration with Jeff 
Browning of Biogen) the structure of the human 
secretory phospholipase A2 that is associated with 
both acute and chronic inflammation. This study 
contrasts the free enzyme with the enzyme in a 
complex with a transition-state analogue and 
shows that the mechanism of this enzyme con- 
forms to what we have proposed earlier for inter- 
facial catalysis. This structure could provide a 
firm stereochemical platform for anti-inflamma- 
tory drug design. 
In order to function, this class of enzymes must 
attach itself firmly to the surface of the mem- 
brane. Others have shown that the attachment of 
the enzyme to the membrane surface is primarily 
due to electrostatic forces. Our calculations (in 
collaboration with Barry Honig, Columbia Uni- 
versity) of the charge-potential distribution for a 
large series of phospholipase A2 structures ac- 
count nicely for this effect. 
Recently our attention has turned to the trans- 
membrane signal cascade that employs seven- 
helical transmembrane receptors, G proteins, 
and target enzymes involved in either the synthe- 
sis or cleavage of phosphodiester bonds (e.g., 
adenyl cyclase, phospholipase C, cGMP phospho- 
diesterase) . Because of the immediate availability 
of large amounts of pure protein, we have chosen 
to work first on the bovine visual receptor sys- 
tem. Our first goal is to solve a recently obtained 
well-ordered crystal form of T^^ • OTP, the solu- 
ble transducer of the activation signal. We hope 
to extend this work to include complexes of 
Tg„ with the activated receptor (rhodopsin) 
and its target molecule, the 7-subunit cGMP 
phosphodiesterase . 
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