tein. On the other hand, 1-, 2-, and 6-deoxy deriva- 
tives of galactose bind 19-, 500-, and l6-fold, re- 
spectively, less tightly than galactose. Nevertheless, 
high-resolution structure refinements indicate no 
apparent difference in the structures of the com- 
plexes with galactose, 1-deoxygalactose, and 2- 
deoxygalactose, except for the obvious absence of 
corresponding hydroxyl groups on the sugars. 
Refining the atomic structures of the complexes 
of the L-arabinose-binding protein with substrates 
L-arabinose, D-fucose, and D-galactose has led to 
the discovery that bound water molecules, coupled 
with localized conformational changes, can modu- 
late substrate specificity and affinity This suggests 
that there is scope for designing analogues, inhibi- 
tors, or drugs with functional groups (e.g., hy- 
droxyl) capable of displacing bound water mole- 
cules in the ligand-binding sites of proteins and 
enzymes. 
C. Peptide deletions and foreign epitope insertion. 
Through recombinant technology, two mutants of 
maltose-binding protein, each with a deletion of a 
different peptide segment, have been obtained. 
Also, the C3 neutralizing epitope for VPl coat pro- 
tein of type 1 poliovirus has been inserted into one 
of these deletions. All three mutant proteins have 
been purified and crystallized. The mutations have 
PUBLICATIONS 
little effect on the transport activity of the mutant 
strains or on the sugar-binding activity of purified 
mutant proteins. Structural analysis is being under- 
taken to understand how the protein molecule can 
accommodate these large alterations and how the 
immunogenicity of a foreign epitope is preserved. 
The use of the maltose-binding protein as a vector 
for immunologically active peptides offers possibili- 
ties for a generation of vaccines from a nonpatho- 
genic source. 
IV Calmodulin. 
The structure of a recombinant Drosophila 
melanogaster calmodulin has been refined at 2.15 
A resolution to an R factor of 0.22. 
The structure of a recombinant calmodulin miss- 
ing two residues in the central helix has been de- 
termined and is being refined. Because the loss of 
two central helix residues leads to a loss of activity 
but the loss of three results in near normal activity, 
the orientation of the two calcium-binding domains 
at the ends of the helix seems to be more impor- 
tant for function than the helix itself 
Dr. Quiocho is also Professor of Biochemistry and 
of Molecular Physiology and Biophysics at Baylor 
College of Medicine. 
Articles 
Jacobson, B.L., and Quiocho, F.A. 1988. Sulfate-binding protein dislikes protonated oxyacids. A molecular ex- 
planation. J Mol Biol 204:783-787. 
Kim, H.-S., Wilson, WK., Needleman, D.H., Pinkenon, F.D., Wilson, D.K. , Quiocho, F.A. , and Schroepfer, G.J., 
Jr. 1989. Inhibitors of sterol synthesis. Chemical synthesis, structure, and biological activities of (25R)- 
3P,26-dihydroxy-5a-cholest-8(l4)-en-15-one, a metabolite of 3P-hydroxy-5a-cholest-8(l4)-en-15-one. 
J Lipid Res 30:247-261. 
Quiocho, F.A. 1988. Molecular features and basic understanding of protein-carbohydrate interactions: the 
arabinose-binding protein-sugar complex. Curr Top Microbiol Immunol 139:135-148. 
Sack, J.S., Saper, M.A., and Quiocho, F.A. 1989. Periplasmic binding protein structure and function. Refined 
x-ray structures of the leucine/isoleucineA^aline-binding protein and its complex with leucine./ A/o/ Biol 
206:171-191. 
Sack, J. S., Trakhanov, S.D., Tsigannik, I.H., and Quiocho, F.A. 1989. Structure of the L-leucine-binding protein 
refined at 2.4 A resolution and comparison with the Leu/IleA'^al-binding protein structure. / Mol Biol 
206:193-207. 
Vyas, N.K. , Vyas, M.N., and Quiocho, F.A. 1988. Sugar and signal-transducer binding sites of the Escherichia 
coli galactose chemoreceptor protein. Science 242:1290-1295. 
Wilson, D.K. , Wilson, WK., Quiocho, F.A. , and Schroepfer, G.J., Jr. 1988. Concerning the structure of 3(3- 
benzoyloxy-5^-cholesta-8,l4-diene, a major byproduct in the chemical synthesis of 5a-cholest-8(l4)-en- 
3p-ol-15-one. Chem Phys Lipids 47:273-282. 
Continued 
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