local twofold symmetry, per asymmetric unit. To 
date, diffraction data from native crystals and from 
seven candidates for heavy-atom derivatives have 
been collected. One of the derivatives appears to be 
useful for phasing. Attempts to extend these studies 
to human Rnasin, and to complexes of porcine and 
human Rnasin with ribonuclease A, are under way. 
SecA Protein from Escherichia coli 
The SecA protein is a central component of the 
machinery that performs protein export through the 
inner membrane of E. coli. It consists of a single 
polypeptide chain of 901 amino acids. Recent find- 
ings indicate that it binds signal peptides, has 
ATPase activity, and can associate with membranes 
or with integral membrane protein complexes. Dr. 
Donald B. Oliver and his colleagues (State Uni- 
versity of New York at Stony Brook) provided pu- 
rified SecA protein and, later, raw material for 
purification. 
Well-shaped crystals were grown, but they do not 
exceed 0.1 mm in any dimension and do not pro- 
duce a measurable diffraction pattern with a labora- 
tory x-ray source. Investigation of the crystal by 
electron microscopy revealed that the unit cell is 
very large, containing probably eight molecules in 
the asymmetric unit, but the packing is nevertheless 
very loose. 
Currently, the crystallization experiments with 
various truncated forms of the SecA protein 
continue. 
Other Projects 
The subjects of additional projects include the cat- 
alytic domain of human HMG-CoA (3-hydroxy-3- 
methylglutaryl coenzyme A) reductase, UvrA and 
GroES from E. coli, the knob protein from adenovi- 
rus, cytochrome b/Cj complexes from Rhodospiril- 
lum rubrum and beef heart mitochondria, the pho- 
tosynthetic reaction center from Rhodobacter 
capsulatus, vertebrate phosphofructokinases, and 
bovine rab3A. 
Dr. Deisenhofer is also Regental Professor, 
Holder of the Virginia and Edward Linthicum Dis- 
tinguished Chair in Biomolecular Science, and 
Professor of Biochemistry at the University of 
Texas Southwestern Medical Center at Dallas. 
Articles 
Boddupalli, S.S., Hasemann, C.A., Ravichandran, 
K.G., Lu, J.-Y., Goldsmith, E.J., Deisenhofer, J., 
and Peterson, J.A. 1992. Crystallization and pre- 
liminary x-ray diffraction analysis of P450,erp and 
the hemoprotein domain of P4 500^, 3, enzymes 
belonging to two distinct classes of the cy- 
tochrome P450 superfamily. Proc Natl Acad Set 
USA 89:5567-5571. 
Deisenhofer, J. , and Michel , H . 1991. Structures of 
bacterial photosynthetic reaction centers. Annu 
Rev Cell Biol7A-25. 
Treutlein, H., Schulten, K., Briinger, A.T., Kar- 
plus, M., Deisenhofer, J., and Michel, H. 1992. 
Chromophore-protein interactions and the func- 
tion of the photosynthetic reaction center: a mo- 
lecular dynamics study. Proc Natl Acad Sci USA 
89:75-79. 
BIOPHYSICAL GENETICS OF PROTEIN STRUCTURE AND FOLDING 
Robert O. Fox, Ph.D., Associate Investigator 
Dr. Fox and his colleagues are investigating the 
role of the amino acid sequence in determining the 
folding pathways and the final detailed three- 
dimensional structure of globular protein mole- 
cules. Several experimental approaches are under 
development to investigate the "structure" of pro- 
tein molecules in the unfolded and molten globule 
states. The laboratory also focuses on the role of 
amino acid sequence in determining turn and loop 
structures in globular proteins, using staphylococ- 
cal nuclease as a model system. 
Mapping Structure in the Unfolded 
and Molten Globule States of Proteins 
Many protein molecules fold into defined three- 
dimensional structures spontaneously and rapidly 
upon completion of synthesis in vivo or upon re- 
moval of chemical denaturants in vitro. Nonnative 
states of proteins that are thought to represent steps 
on the protein-folding pathway can be populated at 
equilibrium. Under native conditions, fragments of 
proteins, such as staphylococcal nuclease, display a 
moderately compact state without applicable sec- 
STRUCTURAL BIOLOGY 469 
