The research team, led by David Price, Ph.D., UI professor of biochemistry, and Tahir Tahirov, Ph.D., professor of structural biology at the Eppley Institute at UNMC, combined expertise in 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.
The structure shows how Tat latches on to this particular human protein and how the interaction alters the shape of the human protein. The study is published in the June 10 issue of the journal Nature.
"We have solved the long sought-after structure of an important HIV protein," Price said. "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."
This distinction is important 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.
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 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.
In addition to Price and Tahirov, the research team included Nigar Babayeva at UNMC and UI researchers Katayoun Varzavand, Jeffrey Cooper and Stanley Sedore. The study was funded by grants from the National Institutes of Health.
Jennifer Brown | Newswise Science News
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
19.07.2018 | Materials Sciences
19.07.2018 | Earth Sciences
19.07.2018 | Life Sciences