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!
Magic number colloidal clusters
13.12.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
Record levels of mercury released by thawing permafrost in Canadian Arctic
13.12.2018 | University of Alberta
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.
Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
13.12.2018 | Life Sciences
13.12.2018 | Physics and Astronomy
13.12.2018 | Earth Sciences