Quarterly Reviews of Biophysics

Research Article

Trends and Challenges in Experimental Macromolecular Crystallography

N. E. Chayena1*, T. J. Boggona2, A. Cassettaa2§, A. Deacona2*, T. Gleichmanna2§, J. Habasha3, S. J. Harropa2 p1, J. R. Helliwella2*, Y. P. Nieha2, M. R. Petersona2, J. Rafterya2, E. H. Snella2* p2, A. Hädenera3, A. C. Niemanna3, D. P. Siddonsa4, V. Stojanoffa4, A. W. Thompsona5a6, T. Ursbya6 and M. Wulffa6

a1 Biophysics Section, Blackett Laboratory, Imperial College of Science, Technology and Medicine, London, SW7 2BZ, UK

a2 Chemistry Department, University of Manchester, Manchester, M13 9PL, UK

a3 Chemistry Department, University of Basle, Switzerland

a4 National Synchrotron Light Source, Brookhaven National Laboratory, Upton, USA

a5 EMBL, Avenue des Martyrs, Grenoble Cedex, France

a6 ESRF, BP220, Grenoble Cedex, France

Macromolecular X-ray crystallography underpins the vigorous field of structural molecular biology having yielded many protein, nucleic acid and virus structures in fine detail. The understanding of the recognition by these macromolecules, as receptors, of their cognate ligands involves the detailed study of the structural chemistry of their molecular interactions. Also these structural details underpin the rational design of novel inhibitors in modern drug discovery in the pharmaceutical industry. Moreover, from such structures the functional details can be inferred, such as the biological chemistry of enzyme reactivity. There is then a vast number and range of types of biological macromolecules that potentially could be studied. The completion of the protein primary sequencing of the yeast genome, and the human genome sequencing project comprising some 105 proteins that is underway, raises expectations for equivalent three dimensional structural databases.

Correspondence:

p1 Current address: School of Physics, University of New South Wales, Kensington, Australia.

p2 Current address: NASA, Code ES76, Building 4464, Marshall Space Flight Center, Huntsville, Alabama 35812, USA.

Footnotes

§ EU Host Institute Fellows in Manchester.

Current address: ESRF, BP220, Grenoble Cedex, France.

* The email addresses of the principal authors to whom correspondence should be sent are: John.Helliwell@man.ac.uk, N.Chayen@ic.ac.uk, Eddie.Snell@msfc.nasa.gov, Ashley@spec.ch.man.ac.uk