Protein crystallography in drug discovery

The rational, structure-based approach has become standard in present-day drug design. As a consequence, the availability of high-resolution structures of target proteins is more often than not the basis for an entire drug development program. Protein structures suited for rational drug design are almost exclusively derived from crystallographic studies, and drug developers are relying heavily on the power of this method. Here, researchers from leading pharmaceutical companies present valuable first-hand information, much of it published for the first time. They discuss strategies to derive high-resolution structures for such important target protein classes as kinases or proteases, as well as selected examples of successful protein crystallographic studies. A special section on recent methodological developments, such as for high-throughput crystallography and microcrystallization, is also included. A valuable companion for crystallographers involved in protein structure determination as well as drug developers pursuing the structure-based approach for use in their daily work.

Preface.

A Personal Foreword.

List of Contributors.

1. Molecular Recognition of Nuclear Hormone Receptor Ligand Complexes (Robert E. Babine).

2. Kinases (Jerry L. Adams, James Veal, and Lisa Shewchuk).

3. The Proteasome as a Drug Target (Tsunehiro Mizushima and Tomitake Tsukihara).

4. Antibiotics and the Ribosome (Jeffrey L. Hansen).

5. Structure Based Design of Cathepsin K Inhibitors (Daniel F. Veber and Maxwell D. Cummings).

6. Structure Based Design of Potent and Selective Cdk4 Inhibitors (Teruki Honma).

7. Crystallization and Analysis of Serine Proteases with Ecotin (Sandra M. Waugh and Robert J. Fletterick).

8. X ray Crystallography in the Development of Orthogonal Ligand Receptor Pairs (Donald F. Doyle and Lauren J. Schwimmer).

9. Engineering Proteins to Promote Crystallization (Lei Jin and Robert E. Babine).

10. High throughput Crystallography (Harren Jhoti).

11. Micro Crystallization (Carl L. Hansen, Morten Sommer, Kyle Self, James M. Berger, and Stephen R. Quake).

Subject Index.