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Hijacking HIV protein rendered in 3-D

U. IOWA (US)—Creation of a three-dimensional picture of an important protein that is involved in how HIV is produced in human cells may help researchers design drugs that can prevent the virus from reproducing.

Researchers combined protein chemistry and X-ray crystallography—a technique for observing protein structures—to produce the first crystal structure of the HIV protein called Tat.

The structure shows Tat attached to the human protein (P-TEFb) that the virus hijacks during infection.

“We have solved the long sought-after structure of an important HIV protein,” says David Price, professor of biochemistry at University of Iowa.

“Now that we know the details of the interaction between Tat and P-TEFb, it may be possible to design inhibitors that target P-TEFb only when it is interacting with Tat.”

The distinction is important, the researchers say, because although inhibiting P-TEFb blocks replication of the HIV virus, P-TEFb is a vital protein in human cells and inhibiting it kills cells.

If an inhibitor could be designed that distinguishes between the P-TEFb attached to Tat and the form that is normal in human cells, that drug might target HIV replication without harming normal cell function.

The study is published in the June 10 issue of the journal Nature.

Such compounds could be useful in combination with existing anti-HIV drugs to further reduce viral levels in HIV-infected individuals.

In addition, drugs that target P-TEFb may also be useful in treating drug-resistant HIV, which is a growing problem, the researchers say.

The HIV virus mutates very easily and can develop resistance to current drugs that target viral proteins. Targeting a human protein like P-TEFb that the virus needs but cannot mutate may be a successful strategy to counter drug-resistant HIV.

Researchers at the University of Nebraska contributed to the study.

More news from the University of Iowa: http://news.uiowa.edu/

Creation of a three-dimension picture of an important protein that is involved in how HIV is produced in human cells may help researchers design drugs that can prevent the virus from reproducing.

Researchers combined protein chemistry and X-ray crystallography—a technique for observing protein structures—to produce the first crystal structure of the HIV protein called Tat.

The structure shows Tat attached to the human protein (P-TEFb) that the virus hijacks during infection.

http://www.news-releases.uiowa.edu/2010/June/060910HIV-protein.html

“We have solved the long sought-after structure of an important HIV protein,” says David Price, professor of biochemistry at University of Iowa.

“Now that we know the details of the interaction between Tat and P-TEFb, it may be possible to design inhibitors that target P-TEFb only when it is interacting with Tat.”

The distinction is important, the researchers say, because although inhibiting P-TEFb blocks replication of the HIV virus, P-TEFb is a vital protein in human cells and inhibiting it kills cells.

If an inhibitor could be designed that distinguishes between the P-TEFb attached to Tat and the form that is normal in human cells, that drug might target HIV replication without harming normal cell function.

http://www.nature.com/nature/journal/v465/n7299/abs/nature09131.html

The study is published in the June 10 issue of the journal Nature.

Such compounds could be useful in combination with existing anti-HIV drugs to further reduce viral levels in HIV-infected individuals.

In addition, drugs that target P-TEFb may also be useful in treating drug-resistant HIV, which is a growing problem, the researchers say.

The HIV virus mutates very easily and can develop resistance to current drugs that target viral proteins. Targeting a human protein like P-TEFb that the virus needs but cannot mutate may be a successful strategy to counter drug-resistant HIV.

Researchers at the University of Nebraska contributed to the study.

More news from the University of Iowa: http://news.uiowa.edu/

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