Download Getting the inside running on enzymes

Getting the inside running on enzymes
A UC biomolecular scientist is
looking at how enzymes work and
the chemical reactions that sustain
human existence.
Professor Emily Parker (Chemistry) has received
Marsden funding of $860,000 over three years to
study enzymes — how they work and how they
can be regulated.
Parker says her team is working on
understanding how communication networks
in proteins support the transmission of signals
between different sites on an enzyme molecule.
“The key focus of the research is about
fundamentally understanding the network
and how it evolved. Can we design a protein
to be regulated in a similar way because we
understand fundamentally the mechanisms in
which this enzyme activity is controlled by the
regulator?
“The particular enzyme that we are looking at is
a bacterial enzyme, which is part of a pathway
that makes an amino acid called leucine. Amino
acids are required by cells to make new proteins
and humans don’t actually have that enzyme —
we get leucine from the proteins that we eat. It is
an essential part of our diet.
“Plants and micro-organisms make leucine
themselves, so the enzyme I am looking at is
found in plants and micro-organisms,” says
Parker.
Parker says all living systems rely on biological
“There is a possibility of
using advanced protein
engineering techniques
for sensing applications
or understanding the
way in which we can turn
molecules or biochemical
pathways on and off.
These findings may also
inform the design of new
antibiotic therapies.”
chemical reactions and the rate at which the
chemical reaction takes place needs to be
regulated and controlled.
“You don’t want an enzyme working to make
a product that a cell doesn’t need. You need to
regulate enzyme activity. There is a vast complex
process to the mechanisms that are available for
enzymes to work.
“The enzymes I primarily work with are found in
pathogenic bacteria so there are some overlaps
where we can target these enzymes for the
treatment of bacterial diseases. If we understand
them in more detail we have a better chance at
producing inhibitors.”
Parker says the focus of the research is on the
part of the enzyme that controls its regulation
and appears to act like a molecular pendulum.
The motion of this pendulum is thought to
control the enzyme activity.
“We think that the pendulum arm can rock back
and forth, and that rocking changes in frequency
or amplitude in response to the binding of the
regulator molecule.
“So what we are going to do is prove that there
is a pendulum action and see how this changes
the activity of the enzyme. This molecular level
understanding is difficult to probe and we are
using different techniques to probe the way it
works.”
Parker says a knowledge of enzyme and protein
communication networks and the importance
of the mechanisms of regulation is vital for
understanding how biological molecules may be
used as sensors.
She says there are many benefits in the work.
“There is a possibility of using advanced protein
engineering techniques for sensing applications
or understanding the way in which we can turn
molecules or biochemical pathways on and off.
These findings may also inform the design of
new antibiotic therapies.”
Research supported by:
• Marsden Fund
By Charlene Smart
Professor Emily Parker
Research Report 2014
21