The enzyme is human kynurenine aminotransferase II (KAT II), which regulates the activity of the neurotransmitter system that is activated by glutamate, the most common neurotransmitter in the brain.
Qian Han, a research scientists in biochemistry at Virginia Tech; Howard Robinson, a biologist at Brookhaven; and Jianyong Li, associate professor of biochemistry at Virginia Tech, report their findings in the article, “Crystal structure of human kynurenine aminotransferase II,” in the Feb. 8 issue of the Journal of Biological Chemistry (www.jbc.org/).
Li, who is corresponding author, explained that learning and memory depend upon glutamate; however, over stimulation will lead to neuron death and is one cause of such neurodegenerative diseases Parkinson’s and Alzheimer’s.
“The product of KAT II is kynurenic acid (KA) that is a noncompeting binder of the glutamate receptors. Its binding to the glutamate receptors reduces stimulation. So it (KA) has a regulatory effect,” Li said. “It is considered protective – although too much is also a problem,” he said.
Before scientists can target KAT II as a treatment, they have to know how it works. Part of the challenge was solved when the DNA sequence of KAT II was determined, but knowing the code is not enough. How proteins pass their critical messages also depends upon their shape. Imagine proteins as curls of ribbons with each unique fold as important to the messages they convey as the sequences of letters in their genetic code.
Han, Robinson, and Li succeeded in determining both the unbound protein and its complex three-dimensional structures of KAT II. The structure in complex with kynurenine reveals the almost ephemeral linkages of the KAT II enzyme with its substrate.
“Now we know what it looks like, we can determine how it works and do research into how to manipulate the protein,” Li said. “We have provided a molecular basis for biochemical regulation of this critical regulator.”
The article reports on Han’s research to crystallize KAT II in combination with a substrate. Robinson used a synchrotron to create X-ray diffraction patterns to reveal atomic and molecular associations within the crystal, which allowed Han and Li to do phase determination and an iterative process of model building and refinement and eventually describe the structure.
Susan Trulove | EurekAlert!
New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg
Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
24.02.2017 | Life Sciences
24.02.2017 | Life Sciences
24.02.2017 | Trade Fair News