Three-dimensional structures of proteins by x-ray crystallographic analysis
Knowledge
of the molecular structure of an enzyme is critically important in
understanding its function, and x-ray crystallography is, to date, the
most powerful technique available for obtaining such information.
Research interest in this laboratory focuses on enzymes involved in
carbohydrate metabolism.
The biological importance of
carbohydrates cannot be overstated for they are essential elements in
nearly every physiological process and represent the most abundant
biomolecules in living systems. Apart from their role in providing
metabolic energy, carbohydrates are involved in a wide range of
biological processes including the immune response, cell-cell
interactions, fertilization, and cell adhesion, among others.
Presently we are continuing our x-ray structural and biochemical
analyses of the four enzymes that constitute the Leloir pathway for
normal galactose metabolism. Defects in the genes encoding these
enzymes can lead to the diseased state referred to collectively as
galactosemia. We have also initiated structural studies on the
proteins in Saccharomyces cerevisiae that regulate transcription of the genes the encode these four enzymes.
Another
area of research interest is in the structure and function of enzymes
involved in the synthesis of the unusual deoxysugars, tyvelose and
desosamine. Tyvelose is a 3,6-dideoxyhexose that occurs in the O-antigens
of some Gram-negative bacteria and has been speculated to play a role
in the pathogenicity of these organisms. Desosamine is a
3-amino-3,4,6-trideoxyhexose found in certain macrolide antibiotics
such as the commonly prescribed erythromycin. The addition of unusual
deoxysugars such as D-desosamine to such polyketide antibiotics
provides or enhances their biological activity.