College of LAS « Illinois

Chemistry

Roll Out the Barrel Structure

Most living organisms are composed of a set of 20 amino acids, which are the so-called basic building blocks of life.

These vital compounds are produced in a biological assembly line in which molecules are added or removed by enzymes until the desired compound is formed. Scientists at U of I are using molecular dynamics simulations to better understand this crucial assembly process. In recent simulations of the amino acid histidine, they have shown how one enzyme may use its "barrel structure" as a channel to guide the movement of small molecules involved in the assembly. This is the first time scientists have suggested that this enzyme may operate in the same fashion as do membrane proteins.

The simulations by chemist Zaida Luthey-Schulten, graduate student Rommie Amaro, and Emad Tajkhorshid, assistant director of theoretical biophysics research at U of I's Beckman Institute, focus on the fifth step in histidine synthesis in which two proteins (hisH and hisF) are shown coming together and reacting, with an ammonia molecule being released from the hisH protein. The molecule enters a narrow channel that runs down the center of the so-called alpha-beta barrel enzyme and is used in a reaction at the active site on the hisF protein.

"Imagine that you need to move an object from one point to another, but there is a mountain in the way," says Amaro. "You could drive over or around it, or you could make a tunnel and drive through it. The tunneling option is what appears to be happening in the fifth step." The simulations show that this is indeed possible and energetically favorable.

October 2003