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Biotechnology advances allow control of protein activity

By Christopher Golis

November 19, 2002 9:00 pm

Researchers at UCLA, in collaboration with scientists at Duke
University and Sandia National Laboratories, have made an advance
in modifying biochemical systems.

In an article published in the November issue of Nature
Materials, researchers reported that they could modify a naturally
occurring protein by adding an on/off switch, which allows it to be
deactivated by the addition of a single atom.

The protein, ATPase, exists naturally in all living cells and
plays a central role in cellular energy metabolism by turning like
a water wheel, generating chemical energy. The modification
represents an artificial method of controlling the protein activity
without disturbing it’s natural function.

UCLA professor Carlo Montemagno, the new chairman of the
Department of Bioengineering, heads this research group and said
that this work “demonstrates a new modality for controlling
protein activity.”

Dr. Homme Hellinga, a professor of biochemistry at Duke
University, played an important role in planning for and
characterizing the changes in the modified ATPase.

Using sophisticated software he developed, researchers were able
to identify changes in the genetic code that would produce a
modified ATPase with an additional binding site. This new binding
site made it possible to control the activity of ATPase without
disturbing the natural function of the molecule.

By attaching tiny metal propellers to the rotor of the modified
molecule, the researchers created what was essentially a

“We could build all sorts of interesting devices that
could transport materials along a track at the nano level,”
Hellinga said.

While the development of the motor switch may have direct
application to biotechnology, the true innovation is the process by
which it was created.

“This provides a general mechanism for controlling protein
activity without making changes to the secondary and binding sites
responsible for primary function,” Montemagno said.

Building upon the revolution in genetics and microbiology of the
past couple decades and making use of advances in protein modeling,
researchers can now engineer useful changes in natural biochemical

“We are in a very fertile time for taking the advances of
the last 10 to 15 years and combining them in a synergistic
manner,” he said.

Hellinga agreed.

“This technology has enormous ramifications that we are
just beginning to realize.”

In the coming decades, bioengineered technology will make use of
naturally evolved biological systems to create microscopic devices
and new materials with embedded functionality.

Using modified proteins, scientists could create drug delivery
systems that release medication directly to affected tissues, or
that react to the temperature or chemical environment.

Using biochemicals that react to light, moisture, or the
presence of toxins, smart materials could be constructed, which
react to stimuli by changing their flexibility, permeability or

For example, this technology might make it possible to construct
an anti-fever implant that detects fever and releases
anti-inflammatory drugs in response.

While such ideas may now seem like science fiction, they
“may in five to 10 years become science fact,”
according to Hellinga.

The diverse application possibilities for this technology is
reflected in the diversity of the funding support that Montemagno

In addition to support from the National Science Foundation and
the National Institute of Science and Technology, groups like NASA,
the Department of Energy, the Office of Naval Research and DARPA
are interested in the possibilities that this technology has for
smart materials.

The National Institution of Health is also supporting the
research, and is interested in its biomedical potential in direct
treatment, diagnosis and powerful medical devices that incorporate
embedded functionality.

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Christopher Golis
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