Book of Abstracts: Albany 2003
June 17-21 2003
Structural Genomics of Human Proteins: Concept, Pitfalls, Achievements
The term "structural genomics" is used to characterize genome-driven structural studies of proteins and other biological macromolecules. In structural genomics projects, target molecules are chosen according to a broad and general set of criteria, and their structure analysis is ideally carried out in a high-throughput, factory-like mode (1). Structural genomics programs are currently being executed in various countries, notably in North America, Japan and Europe (2).
A Berlin-area structural genomics effort, the Protein Structure Factory (3), using both NMR spectroscopy and X-ray crystallography for the structure analysis of human proteins of presumed structural novelty and medical relevance. The approach to high-throughput protein structure analysis taken by this project (4) (see scheme below) will be described in some detail. Special emphasis will be placed on crucial issues of the automation of expression cloning in various host systems, protein purification and crystallization, as well as the design and implementation of new synchrotron-based resources for X-ray diffraction experiments (5). Comparing first results from the Protein Structure Factory with data published by others, the different approaches towards structural genomics, their implementation, achievements and limitations will be discussed.