Professor of Biochemistry & Molecular Biology
PO Box 980614
Richmond, VA 23298-0614
Email: xrdproc@hsc.vcu.edu
Telephone: 804-828-6139
Education
- AB, Princeton University, 1963
- Ph.D., Chemistry,University of California, San Diego, 1968
Post-Doc
- Postdoctoral Fellow, NIH, University of California, San Diego, 1968-1969
- Postdoctoral Fellow, NIH, MRC Laboratory of Molecular Biology, Cambridge, England, 1969-1971
Research
Structure analysis of biological macromolecules by x-ray crystallography and
computer model building is the focus of the laboratory's work. Our broad
objectives are to understand enzymatic mechanisms and the interactions of
biological macromolecules at the atomic level. We use recombinant DNA methods to
obtain large amounts of proteins for structural studies and for mutagenesis to
test hypotheses for function. We collaborate closely with other research groups
with complementary research approaches and mutual interests.
In collaboration with the Schirch group, we have determined the structure of
serine hydroxymethyltransferase, a central enzyme of one carbon metabolism,
which requires both vitamin b6 and folate cofactors. We are examining complexes
of this enzyme and its site mutants with substrates, products and inhibitors to
investigate its mechanism. We are also studying a class of proteins, the
serpins, which are inhibitors of serine proteinases, important enzymes in many
physiological processes, including blood clotting and fibrinolysis. Serpins
undergo an unusual structural transition in the formation of very stable
complexes with their target proteinases. We are studying the structure and
mechanism of several serpins using crystallographic, molecular modeling and site
directed mutagenesis techniques in collaboration with U. Desai of the Dept. of
Medicinal Chemistry. The serpin alpha-1-antichymotrypsin plays a role in the
etiology of Alzheimer's disease, and we are studying its interaction with the
Alzheimer's amyloid peptide to which it binds. In collaboration with K.
Reynolds of the Dept. of Medicinal Chemistry, we are studying studying the
structure of a critical enzyme of fatty acid biosynthesis, both to understand
its mechanism and to try to develop small compounds as potential leads for
antibiotic development. We recently began a project to determine the structure
of an RNA-binding protein involved in the maturation of ribosomal RNA.
Publications
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