Professor of Biochemistry & Molecular Biology
PO Box 980614
Richmond, VA 23298-0614
Email: chlebows@hsc.vcu.edu
Telephone: 804-828-1023
Education
Ph.D., Case Western Reserve University, 1969
Post-Doc
- Research Associate, University College London, 1971
- Research Fellow, Yale University, 1976
Research
Research interests are focused on assessing the mechanisms
that modulate protein structure, control protein
expression, and regulate enzymatic activity in vitro
and in vivo. Our investigations center on the E.
Coli alkaline phosphatase. A wide variety of methods
are employed in our investigations including biophysical
approaches (e.g. nuclear magnetic resonance, electron
microscopy, Fourier-Transform infrared, circular
dichroism, X-ray crystallography), traditional methods
of protein chemistry and enzymology, as well as the
application of molecular biology techniques.
The dimeric Zn(II) metalloenzyme alkaline
phosphatase is found in the periplasmic space of the
gram-negative E. Coli bacterium. The elements of the
biosynthestic pathway leading to the information and
localization of the mature protein provide an accessible
model system representative of the complex pathway
of protein maturation found in all organism. These
include the mechanisms of transcriptional and translational
control, transmembrane vectorial transport, the proteolytic
event(s) which occur after compartmentalization to
render this process irreversible, folding of the polypeptide
chain, the binding of prosthetic groups, subunit assembly,
and additional modification steps. Our most recent
investigations have led to the discovery of an adenylated
peptide, which is bound to the freshly isolated protein.
Association of this compound induces structural alterations
in the enzyme. Investigations of a broad regulatory
function for this unusual peptide are in progress.
Deletions of segments of the amino terminal portion
of the mature protein by either limited proteolysis
or deletion mutagenesis subtly alter the structural
and functional properties of alkaline phosphatase.
Complete characterization of these truncated forms
of the enzyme provides insight into factors important
in influencing protein folding, subunit association,
and allosteric effects. Solution of the crystal structure
of the enzyme from which the amino terminal decapeptide
has been deleted from both subunits in currently underway.
Publications
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