“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.

Learn more about Jianyong Li’s group here: (http://www.biochem.vt.edu/faculty.php?lname=Li&view=yes)

Access an article abstract here: http://www.jbc.org/cgi/content/abstract/M708358200v1. Address correspondence to: Jianyong Li, Department of Biochemistry, Virginia Tech, Blacksburg, Va 24061, Tel: 540-231-1182; E-mail: lij@vt.edu