Case Western Reserve University chemist takes on HIV-1 virus with $1M support from NIH

een known for years that the subunits can come apart, mostly everyone has ignored this fact in research, said Barkley.

She sees the potential of interfering with how the subunits come together as one way of thwarting the spread of the virus.

"We know that the subunits have to be together to catalyze DNA synthesis, and that the second generation RT inhibitors can alter how tightly the two subunits stick together," Barkley explains. "We think the way that the subunits come together play a role in the protein's -- and thus the patient's -- resistance to drugs and in how the drugs inhibit the DNA synthesis."

"No one has looked at how these pieces come together and how it is related to the catalysis other than they knew it had to happen for the virus to grow. This is where we started working," she said.

Barkley began work on the HIV-1's reverse transcriptase enzyme in 1998 through collaboration with Stuart Le Grice, the former director of the Center for AIDS Research at the Case School of Medicine.

She said researchers have crystallized the RT and then looked its 3-dimensional structure using x-ray diffraction, but according to Barkley, the structure does not tell how it works.

She will collaborate with Patrick Wintrode in the Case School of Medicine's department of physiology and biophysics, who uses a new technique that tracks the fast exchanges of protons for deuterons on the protein's surface. This technique will provide another view of how the protein functions and as well as answers to what happens when the two subunits are apart and then come together.

"It has been difficult," said Barkley. "Everything we have done with this protein is that you try it and think it is going to be a straightforward method that is used on many other proteins and will work on this one, but it doesn't work as expected."

This new approach may be the answer to understanding the protein, she said.'"/>

Contact: Susan Griffith
Case Western Reserve University

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