Structural Biology

Work in our lab involves Structural Biology, a specialty within the broader field of Biochemistry, much like glycobiology or molecular biology also fall under the umbrella of Biochemistry. The distinction between Structural Biology and Biochemistry is subtle. The tools of structural biology enable a scientist to understand important biochemical processes at atomic and molecular level. A structural biologist does not simply want to understand what a protein does. Rather, we aim to understand how it performs its function. We do not just want to know that an enzyme is a protein tyrosine kinase that is involved in signal tranduction; we want to understand why that enzyme targets specific residues on specific proteins and not any of the other proteins in the cell. And then we want to know how that phosphorylation event changes the activity of the downstream protein.

We want to know that a protein is a transmembrane channel that is involved in uptake of specific ions. But we also want to understand what features allow it to differentiate between calcium ions and potassium ions and what features dictate the direction of the transport. What drives a structural biologist, and what guides our studies, is a fascination for the ability of macromolecular machines to perform such a wide range of duties.

To unravel these molecular mysteries, we use many tools. Among them are biochemical and molecular techniques to characterize proteins and protein activity. We use biophysical tools that can provide measurements of binding affinities and genetic tools that demonstrate the effect of mutations or deletions of important genes. And we use structural techniques that allow us to determine the arrangement of atoms that proteins adopt. This information allows us to develop hypotheses about protein function that we can test with the techniques described above.

All structural biologists are biochemists. And, in fact, most biochemists are structural biologists, whether they personally determine new structures or not. We all strive to understand the molecular basis of important biological processes. What is the function of a novel protein and how does it perform that task? What goes wrong that causes disease? And what can we do to diminish the negative consequences of disease.

Specific projects in our lab focus on the structural biology of natural product biosynthesis and are described on the next few pages.