Tables for
Volume F
Crystallography of biological macromolecules
Edited by M. G. Rossmann and E. Arnold

International Tables for Crystallography (2006). Vol. F, ch. 1.3, p. 10   | 1 | 2 |

Section 1.3.1. Introduction

W. G. J. Hola* and C. L. M. J. Verlindea

aBiomolecular Structure Center, Department of Biological Structure, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195-7742, USA
Correspondence e-mail:

1.3.1. Introduction

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In the last hundred years, crystallography has contributed immensely to the expansion of our understanding of the atomic structure of matter as it extends into the three spatial dimensions in which we describe the world around us. At the beginning of this century, the first atomic arrangements in salts, minerals and low-molecular-weight organic and metallo-organic compounds were unravelled. Then, initially one by one, but presently as an avalanche, the molecules of life were revealed in full glory at the atomic level with often astonishing accuracy, beginning in the 1950s when fibre diffraction first helped to resolve the structure of DNA, later the structures of polysaccharides, fibrous proteins, muscle and filamentous viruses. Subsequently, single-crystal methods became predominant and structures solved in the 1960s included myoglobin, haemoglobin and lysozyme, all of which were heroic achievements by teams of scientists, often building their own X-ray instruments, pioneering computational methods, and improving protein purification and crystallization procedures. Quite soon thereafter, in 1978, the three-dimensional structures of the first viruses were determined at atomic resolution. Less than ten years later, the mechanisms and structures of membrane proteins started to be unravelled. Presently, somewhere between five and ten structures of proteins are solved each day, about 85% by crystallographic procedures and about 15% by NMR methods. It is quite possible that within a decade the Protein Data Bank (PDB; Bernstein et al., 1977[link]) will receive a new coordinate set for a protein, RNA or DNA crystal structure every half hour. The resolution of protein crystal structures is improving dramatically and the size of the structures tackled is sometimes enormous: a virus with over a thousand subunits has been solved at atomic resolution (Grimes et al., 1995[link]) and the structure of the ribosome is on its way (Ban et al., 1999[link]; Cate et al., 1999[link]; Clemons et al., 1999[link]).

Macromolecular crystallography, discussed here in terms of its impact on medicine, is clearly making immense strides owing to a synergism of progress in many scientific disciplines including:

  • (a) Computer hardware and software: providing unprecedented computer power as well as instant access to information anywhere on the planet via the internet.

  • (b) Physics: making synchrotron radiation available with a wide range of wavelengths, very narrow bandwidths and very high intensities.

  • (c) Materials science and instrumentation: revolutionizing X-ray intensity measurements, with currently available charge-coupled-device detectors allowing protein-data collection at synchrotrons in tens of minutes, and with pixel array detectors on the horizon which are expected to collect a complete data set from a typical protein within a few seconds.

  • (d) Molecular biology: allowing the cloning, overexpression and modification of genes, with almost miraculous ease in many cases, resulting in a wide variety of protein variants, thereby enabling crystallization of `impossible' proteins.

  • (e) Genome sequencing: determining complete bacterial genomes in a matter of months. With several eukaryote genomes and the first animal genome already completed, and with the human genome expected to be completed to a considerable degree by 2000, protein crystallographers suddenly have an unprecedented choice of proteins to study, giving rise to the new field of structural genomics.

  • (f) Biochemistry and biophysics: providing a range of tools for rapid protein and nucleic acid purification by size, charge and affinity, and for characterization of samples by microsequencing, fluorescence, mass spectrometry, circular dichroism and dynamic light scattering procedures.

  • (g) Chemistry, in particular combinatorial chemistry: discovering by more and more sophisticated procedures high affinity inhibitors or binders to drug target proteins which are of great interest by themselves, while in addition such compounds tend to improve co-crystallization results quite significantly.

  • (h) Crystallography itself: constantly developing new tools including direct methods, multi-wavelength anomalous-dispersion phasing techniques, maximum-likelihood procedures in phase calculation and coordinate refinement, interactive graphics and automatic model-building programs, density-modification methods, and the extremely important cryo-cooling techniques for protein and nucleic acid crystals, to mention only some of the major achievements in the last decade.

Numerous aspects of these developments are treated in great detail in this volume of International Tables.


Ban, N., Nissen, P., Hansen, J., Capel, M., Moore, P. B. & Steitz, T. A. (1999). Placement of protein and RNA structures into a 5 Å-resolution map of the 50S ribosomal subunit. Nature (London), 400, 841–847.
Bernstein, F. C., Koetzle, T. F., Williams, G. J., Meyer, E. F. Jr, Brice, M. D., Rodgers, J. R., Kennard, O., Shimanouchi, T. & Tasumi, M. (1977). The Protein Data Bank. A computer-based archival file for macromolecular structures. Eur. J. Biochem. 80, 319–324.
Cate, J. H., Yusupov, M. M., Zusupova, G. Z., Earnest, T. N. & Noller, H. F. (1999). X-ray crystal structures of 70S ribosome functional complexes. Science, 285, 2095–2104.
Clemons, W. M. J., May, J. L., Wimberly, B. T., McCutcheon, J. P., Capel, M. S. & Ramakrishnan, V. (1999). Structure of a bacterial 30S ribosomal subunit at 5.5 Å resolution. Nature (London), 400, 833–840.
Grimes, J., Basak, A. K., Roy, P. & Stuart, D. (1995). The crystal structure of bluetongue virus VP7. Nature (London), 373, 167–170.

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