Molybdenum
is an essential metal required in all living beings from bacteria to
plants to humans. But as vital as this metal is, no one understood the
importance of its structure until the Faculty of Medicine &
Dentistry’s Joel Weiner and his team at the University of Alberta jumped
on the case.
Molybdenum
plays critical roles in human health. It does not act alone but is
found attached to certain proteins, called molybdenum enzymes, by a very
large organic molecule. The organic molecule that holds the molybdenum
in place in a protein is extraordinarily complex and “expensive” for the
cell to make. But the structure of this molecule should make sense to
scientists now, thanks to Weiner and his research team.
For
starters, the research group found that the molecule occurs in nature
in two forms based on their appearance—flat or distorted. Weiner’s team
was able to show that the distorted form and flat form have very
different functions. The distorted molecule plays a role in the transfer
of electrons to the molybdenum, whereas the flat molecule prepares and
co-ordinates positioning of the enzyme so it can be part of a
biochemical reaction.
“This
is important because molybdenum is so essential throughout biology,”
said Weiner. “We need to understand why the cell goes to all this
trouble.”
The
distorted form is found in proteins involved in metabolic, respiratory
and cardiac diseases. The flat form occurs in a protein required for
brain development, and defects in this protein cause death in infancy.
Understanding of this flat form could help lead to treatment of this
defect.
It
all started for Weiner and his research group in the Department of
Biochemistry about three years ago. Although scientists worldwide had
known the overall structure of molybdenum in proteins for many years, no
one understood why it is so complicated. It was a summer student,
Matthew Solomonson, who noticed that one of the structures holding
molybdenum was very flat while the other group was distorted. As
curiosity-based research goes, the summer student and Weiner’s research
team wondered if it was significant. The answer is yes.
“When
you bring in a new student it’s really good because they have a fresh
way of looking at things,” says Weiner of Solomonson who is now a grad
student at the University of British Columbia.
“This discovery is a major one for my lab and will have a huge impact on molybdenum biochemistry research.”
Now the team will use protein-engineering techniques to change the protein environment around the molybdenum.
“This
is a critical next step,” said Weiner. “We hope to finally start
understanding the chemistry of these enzymes at atomic resolution, and
to modulate their activities to better understand human disease and
explore potential biotechnology and biomedical applications.”
This work is published in the journal Proceedings of the National Academy of Sciences. This study was funded by the Canadian Institutes of Health Research.
Source: University of Alberta
