Crystal Healing - the art of using X-ray crystallography in the search for new drugs.
Inaugural lecture by Prof. Garry L. Taylor at Bath University, 22nd April 1999.

Garry began by reassuring the audience that he wouldn't be talking about "energy medicine", he showed a book on the subject, whose title he'd borrowed, which suggested that for the stress he was feeling at that moment he should be lying on the floor with a quartz crystal on his solar plexus. He found listening to Mozart was more effective! The healing he'd be describing came from designing drugs against proteins whose structures were much more complicated than quartz and which did not crystallise naturally.

After this introduction the talk was in three sections, the first describing what proteins are, then moving on to crystallography and finally on to the sialidase class of enzymes and drug design. In the protein section Garry described the relative sizes of cells, viruses and proteins, explained secondary structure motifs and how the pictures protein crystallographers use relate to the atoms in the structure.

In the crystallography part Garry started by explaining why we need X-rays and crystals to investigate protein structure rather than an ordinary visible light microscope. A brief history of crystallography followed, starting with the Braggs' NaCl in 1915, moving on to the 1962 Nobel prizes for DNA, myoglobin and haemoglobin; then the infamous report of Dorothy Hodgkin's 1964 Nobel prize going to a "British wife" for the structures of penicillin, Vitamin B12 and insulin. The first enzyme structure, lysozyme, was solved by David Phillips in 1965.

Following these introductory sections Garry moved on to work that has been done on the sialidases. Sugars on the surfaces of cells commonly terminate in one called sialic acid and the sialidase enzymes exist to remove this sugar. Garry concentrated on case studies of sialidases from four different organisms. The best studied is that from influenza, the structure was solved in Australia. From knowledge of the active site, compounds were designed to bind more tightly than the natural sialic acid and thus hopefully could be used as drugs against all strains of influenza, relieving us from the necessity of annual vaccinations. Garry used the equivalent enzyme from a paramyxovirus, Newcastle Disease virus, to illustrate the structure solution process. To solve this structure required more than 500 crystals, 150 derivative data sets, 5000000 X-ray intensities and five years of work. While he talked we began to hear music which gradually became louder and as the structure was solved Garry became inaudible under the waves of Wagner's Götterdämmerung crashing around the lecture theatre.

Next came the structure of a sialidase from V. cholerae, the bacterium which causes cholera. This enzyme has extra domains to enable it to hang around in the fast-flowing environment of the small intestine. Finally the story of the South American trypanosome which affects 80 million Latin American people. It has a sialidase enzyme which removes the sialic acid from the host cells to add to its own, helping to disguise it from the immune system. It is an attractive target for drug design; Garry's research group are trying to crystallise this enzyme.

In his concluding remarks Garry made the point that this was only one class of enzymes, the vast genome sequencing effort round the world is opening up a mine for drug companies looking for attractive targets. Finally he thanked his family and research group for their help and support.
Susan Crennell, University of Bath

Page last updated 30 May 1999