enzyme function through X-ray crystallography
Our laboratory uses X-ray crystallography as a chief technique to
study the structure and mechanism of metalloproteins. We focus on
enzymes that contain complex metallocofactors and catalyze challenging
chemical reactions, such as those that use radical-based chemistry
or form organometallic bonds. We are interested in providing detailed
three-dimensional information about the nature of complex metallocofactors
to help understand how protein environment modulates reactivity. Using
X-ray crystallography, we hope to gain insight into the function and
mechanism of nature's complex protein machines.
Over the last few decades, advances in molecular biology, protein
expression and purification, bioinformatics, computing power, and
software development has made possible the structural determination
of not just one enzyme, but several enzymes along an entire pathway.
This has allowed us to better understand the interplay between enzymes
in the production and manipulation of important metabolic molecules
and natural products. Equally as important, these advances have also
enabled us to solve mutiple structures of a single enzyme with bound
substrates, analogs, and products, to acquire a series of "snapshots"
of a single enzyme turnover. With these capabilities, X-ray crystallography
has become a crucial element in studying enzyme mechanism.
From DNA to protein to crystal structure