ABSTRACT
The first protein structure took about three decades to complete, and all protein structures solved in the early years required Herculean efforts. Most aspects of the process were difficult, time consuming, expensive, labor intensive, and problematic. But during the past decade, technological breakthroughs in protein production, crystallization (still the most trying step), data collection, structure solution, and refinement have dramatically altered this picture. Although it is difficult to pick the most significant advance, development of user-friendly synchrotron beamlines for protein crystallography is high on the list. Of course, many classes of proteins-notably, large protein complexes and membrane proteins-often still require years of intense effort and imagination to solve. On the other hand, many soluble globular proteins can now be solved almost routinely. The power of structural studies to advance biological understanding was obvious from the start. Three-dimensional structures have already provided unique insight into macromolecular function and mechanism. Structure has also become an important aid for targeted drug design. Additionally, a “complete” set of structures can provide insights into the architecture of proteins and its relationship to function, as well as protein folding and evolution.
