Barry B. Muhoberac
Phi Beta Kappa
Research
The two main thrusts of this research program are
to understand structure-function relationships that occur in metalloproteins
and in biomembranes.
Metalloproteins are quite diverse in their functions,
which range from electron or ligand transport to catalysis. Different
metals, as well as the specifics of the interaction between the
metal ions and their protein environments, contribute to this diversity.
Structure-function relationships in metalloproteins are investigated
using metal ions as endogenous spectroscopic probes of the sites
of ligand binding and/or catalysis. Studies focus on determining
metal ion coordination that are reduced by ligand or substrate binding,
dimerization, or polyelectrolyte complexation. Links between overall
protein conformation and metal coordination are considered, as well
as the thermodynamic parameters governing the processes mentioned
above.
Drugs and small molecules perturb the structure of biomembranes
through interaction with phospholipids, membrane-bound enzymes,
or both. However, the connection between structural perturbation
and altered enzyme function is often unclear. Structure-function
relationships in biomembranes are investigated by using fluorescence
and electron paramagnetic resonance spectroscopies to quantitate
drug-induced changes in biomembrane structure that are correlated
with alteration in activity of membrane-bound enzymes. Often exogenous
fluorescent probes or spin labels are used to quantitate structural
change, but endogenous tryptophane fluorescence is also followed.
A series of drugs with similar structure but varying hydrophobicity,
charge, and/or steric determinants is used to help elucidate how
such factors modulate drug binding and hence the associate change
in biomembrane function.
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