MU biochemist part of first team to "see" AIDS enzyme
The discovery could change the target of AIDS treatment.
Oct. 10, 2008
An MU researcher is part of the first team to watch the initial formation of HIV.
In a study published in the Oct. 2 issue of Nature magazine, biochemistry professor Chun Tang and four scientists from the National Institute of Diabetes and Digestive and Kidney Diseases used a new technique to watch the joining of two precursors to the HIV-1 protease enzyme, which triggers the release of HIV.
HIV-1 protease helps to create mature proteins that allow the virus to spread to other cells.
The enzyme is one of the primary targets of AIDS treatments. The treatments use other molecules to inhibit the portion of the enzyme that bonds with particles known as substrates. Because HIV-1 protease is constantly mutating, it is resistant to the drugs.
"The virus is constantly mutating, so you want to find more targets to inhibit different states of the virus life cycle," Tang said.
When a person first contracts HIV, the protease is inactive, meaning it will not produce the particles that encourage replication, even when the substrate is present.
According to the report, Tang and the NIDDK scientists discovered the inactive enzyme has a tail of amino acid residues. Using their new technique, they saw the enzyme self-activates by joining the two halves of the tail and cutting it off.
Their technique uses nuclear magnetic resonance, which occurs when nuclei of atoms, like those in the protease, are exposed to both a static field and a moving magnetic field. The protons of the protease molecule have a property called spin, which produces a magnetic field around the protons. The interaction of the NMR magnetic fields with those of the protease protons produces lines to create and image of the protease molecule.
Tang said the paramagnetic waves, which expose molecules to four magnetic fields, helped magnify the site where the protein tails are cut, allowing scientists to view the activation of the enzyme.
Marius Clore, a co-author of the study, said the findings show the importance of the new nuclear magnetic resonance technique in molecular research.
"This process allows us to see important species that are invisible to conventional techniques," he said.
Co-author John Louis is head of the NIDDK division that focuses on protein engineering and chemistry. His team uses information about the protease activation to substances that will inhibit the proteins that allow HIV to bind to a cell in the person's body. Louis said the discovery gives more direction to future AIDS research.
"Basically you are studying the activation of the protease, with the scope that you would study the inhibition of the maturation of the protease," Louis said. "That's the take-home message."
In addition to Chun, Clore and Louis, NIDDK post-doctoral fellow Jeong-Yong Suh and research assistant Annie Aniana co-authored the study, which occurred in July and was accepted for publication in August.