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

International Tables for Crystallography (2012). Vol. F, ch. 1.3, pp. 13-14   | 1 | 2 |

Section 1.3.2. Crystallography and medicine

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:

1.3.2. Crystallography and medicine

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Knowledge of accurate atomic structures of small molecules, such as vitamin B12, steroids, folates and many others, has assisted medicinal chemists in their endeavours to modify many of these molecules for the combat of disease. The early protein crystallographers were well aware of the potential medical implication of the proteins they studied. Examples are the studies of the oxygen-carrying haemoglobin, the messenger insulin, the defending antibodies and the bacterial-cell-wall-lysing lysozyme. Yet, even by the mid-1980s, there were very few crystallographic projects which had the explicit goal of arriving at pharmaceutically active compounds (Hol, 1986[link]). Since then, however, we have witnessed an incredible increase in the number of projects in this area with essentially every major pharmaceutical company having a protein crystallography unit, while in academia and research institutions the potential usefulness of a protein structure is often combined with the novelty of the system under investigation. In one case, the HIV protease, it might well be that, worldwide, the structure has been solved over one thousand times – in complex with hundreds of different inhibitory compounds (Vondrasek et al., 1997[link]).

Impressive as these achievements are, this seems to be only the beginning of medicinal macromolecular crystallography. The completion of the human genome project will provide an irresistible impetus for `human structural genomics': the determination, as rapidly and systematically as possible, of as many human protein structures as possible. The genome sequences of most major infectious agents will be completed five years hence, if not sooner. This is likely to be followed up by `selected pathogen structural genomics', which will provide a wealth of pathogen protein structures for the design of new pharmaceuticals and probably also for vaccines.

This overview, written in late 1999, aims to convey some feel of the current explosion of `crystallography in medicine'. Ten, perhaps even five, years ago it might have been feasible to make an almost comprehensive list of all protein structures of potentially direct medical relevance. Today, this is virtually impossible. Here we mention only selected examples in the text with apologies to the crystallographers whose projects should also have been mentioned, and to the NMR spectroscopists and electron microscopists whose work falls outside the scope of this review. Tables[link] and[link] to[link] provide more information, yet do not claim to cover comprehensively this exploding field. Also, not all of the structures listed were determined with medical applications in mind, though they might be exploited for drug design one day. These tables show at the same time tremendous achievements as well as great gaps in our structural knowledge of proteins from humans and human pathogens.


Vondrasek, J., van Buskirk, C. P. & Wlodawer, A. (1997). Database of three-dimensional structure of HIV proteinases. Nature Struct. Biol. 4, 8.
Hol, W. G. J. (1986). Protein crystallography and computer graphics – toward rational drug design. Angew. Chem. Int. Ed. Engl. 25, 767–778.

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