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Bacteria Protein Structure Discovered
By Monica Bobra
Using SSRL, three scientists from the Salk
Institute for Biological Studies have discovered the three-dimensional
structure of a protein that bacteria use to make anti-cancer,
anti-viral, anti-inflammatory and anti-oxidant compounds. By effectively
engineering this protein, scientists may be able to create new drugs
with therapeutic properties. The Salk Institute scientists reported
their results in the June 16 issue of Nature.
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A schematic
diagram of the Orf2 protein allows scientists to visualize it in
three-dimensional space. The helical structure is known as a PT
barrel. Thin strands of molecules reside within the PT barrel;
the sphere in the protein's core represents magnesium.
(Image courtesy of
Interactions.org) |
The bacterial protein, known as
Orf2, contains a previously unknown structure shaped like a barrel.
Scientists discovered this structure using a process called x-ray
crystallography, a technique in which x-rays, produced by synchrotron
radiation, hit the protein’s atoms and diffract to produce a
two-dimensional pattern. Computers then interpret a set of such patterns
and construct a high-resolution three-dimensional image. Researchers
gathered data at SSRL, the National Synchrotron Light Source (NSLS) at
BNL and the European Synchrotron Radiation Facility.
“Looking at the protein’s structure is like opening up a
clock and understanding how all the parts fit together and work in
unison,” said co-author Joseph Noel. “With x-ray instruments from our
lab at the Salk Institute, we looked at Orf2 from 30 feet away. With
SSRL, we can look at it with a magnifying glass if we need to. That’s an
essential part of the whole process.”
Orf2 is one of a small number in a recently isolated
family of proteins that create compounds with anti-microbial,
anti-cancer, anti-viral, anti-inflammatory and anti-oxidant properties.
It accomplishes this remarkable task by adding hydrocarbons known as
prenyl groups to flat benzene-like molecules. By manipulating Orf2 using
knowledge of its three dimensional shape, scientists could engineer
therapeutic drugs. “When we
first looked at it, very quickly, we thought: this is one of the most
common 3-D folds known in nature,” said Noel, referring to a common
helical protein structure known as a TIM barrel. Soon after, the team
realized Orf2’s shape was incredibly distinctive; its amino acids, which
form the protein’s building blocks, are arranged in an entirely
different manner.
“We currently use the protein as a
surrogate chemist, allowing it to catalyze chemical reactions that would
be difficult or impossible to do with traditional chemistry,” said Noel.
In this way, the researchers slightly modify existing chemicals, which
may lead them to discover new drugs. “We hope to use and engineer the
protein to create novel compounds,” said Stéphane Richard, who helped
make the discovery. In
addition, studying Orf2’s structure allows the scientists to understand
the fundamental process of molecular evolution. The team is analyzing
the amino acid sequence of closely related proteins to understand how
Orf2 has changed over time. “Using laboratory techniques for genetic
manipulation,” said Noel, “we can now make changes to Orf2 and its
relatives in a manner resembling the path that evolution has taken over
the last half a billion years or so.” |
