Featured in the cover article of the April 2004 issue of Structure, University of Virginia School of Medicine researcher Zygmunt Derewenda, Ph.D., describes how his group was able to coax certain proteins to crystallize by carefully altering their surfaces using "targeted mutagenesis." In effect, the technique substitutes a small amino acid for certain large ones. This effectively shrinks bulky groups of atoms on protein surfaces that might otherwise prevent the proteins from crystallizing.
"In order to determine a high-resolution structure of a protein, we need to study it in its crystal form," Derewenda explained. "Yet many proteins do not crystallize easily, or even at all, with current laboratory techniques. Using our approach, we can now make some of these proteins more amenable to crystallization without seriously affecting their overall structure or function."
Already, the crystal engineering technique has helped solve the structures of some particularly stubborn proteins, including the so-called V antigen of Yersinia pestis, the bacterium that causes the plague. Despite numerous attempts, researchers had been unsuccessful in unlocking the secrets of this protein, which plays a key role in the bacterium's ability to cause the plague. Working with Derewenda's group, David S. Waugh, Ph.D., of the NIH's National Cancer Institute in Frederick, Md., was able to crystallize the protein and then determine its structure
Contact: Alisa Zapp Machalek
NIH/National Institute of General Medical Sciences