- Person
- Max Perutz
- Lived
- 1914–2002
- Field
- Molecular biology
- From
- Austrian-British
The story
X-ray crystallography reveals the arrangement of atoms in a crystal from the pattern of spots that X-rays make when they scatter off it. But a diffraction pattern records only half the information needed: the brightness of each spot, not a second property called its phase, and without phases no image of the molecule can be built. In the late 1930s the largest organic molecule whose structure had been solved was tiny compared with haemoglobin, which has a molecular weight of about 64,500. For proteins, the phase problem seemed insurmountable.
Max Perutz, a refugee from Vienna who had come to Cambridge in 1936, began photographing crystals of horse haemoglobin in 1937. He first hoped to crack the structure with a mathematical shortcut called the Patterson function, which meant measuring the intensities of thousands of X-ray spots and running the calculations on punch-card machines. The result, published in 1949, seemed to show interesting features, but they turned out to be misleading.
The breakthrough came in 1953, after more than fifteen years of work. Theory and measurement suggested that a method called isomorphous replacement should work even for large molecules. As luck would have it, a mercury atom attached to one spot on the haemoglobin molecule did not disturb the crystal, but did change some of the X-ray intensities. By comparing patterns from crystals with and without such heavy atoms, Perutz could work out the missing phases, and that year he solved a two-dimensional projection of the structure.
A full three-dimensional picture needed several different heavy-atom derivatives, and it took five more years. Meanwhile his colleague John Kendrew used the same approach to solve myoglobin, a protein a quarter the size of haemoglobin, and Perutz's team completed haemoglobin itself. Perutz and Kendrew shared the 1962 Nobel Prize in Chemistry.
Heavy-atom phasing turned protein crystallography from a hope into a working science. It led directly to the first protein structures and became the foundation on which the structures of enzymes, antibodies and countless other molecules of life were later solved. The European Crystallographic Association's Max Perutz Prize is named in his honour.
Why it matters
Heavy-atom phasing founded structural biology, the field that reveals the shapes of the molecules of life and guides modern drug design.
About Max Perutz
Viennese refugee who spent 22 years solving the structure of haemoglobin, won the 1962 Nobel Prize and built the Cambridge laboratory where molecular biology came of age.
More about Max Perutz
- Max Perutz founded the unit where DNA's shape was foundIn 1947 Max Perutz obtained Medical Research Council support for a small unit to study biological molecules; Watson and Crick built their DNA model there in 1953.
- Max Perutz was also a pioneering glacier scientistIn 1938 Max Perutz joined a three-man expedition to study how snow becomes glacier ice in Switzerland, work that made him an expert on glaciers.
- Perutz explained how haemoglobin delivers oxygenIn 1970 Max Perutz proposed how haemoglobin works as a molecular machine, switching shape to pick up oxygen in the lungs and release it in the tissues.
- Perutz linked haemoglobin's shape to inherited diseaseMax Perutz studied how changes in haemoglobin's amino acids alter its function, hoping to find drugs for genetic blood disorders such as sickle cell anaemia.
- In his eighties, Perutz took on Huntington's diseaseIn his final years Max Perutz studied Huntington's disease, showing that its age of onset is linked to the number of glutamine repeats, which form a 'polar zipper'.
- Perutz led a lab whose scientists shared 12 Nobel PrizesMax Perutz founded and chaired the MRC Laboratory of Molecular Biology in Cambridge from 1962 to 1979; its scientists have shared 12 Nobel Prizes.
- Max Perutz revealed the structure of haemoglobinIn 1959, 22 years after he began, Max Perutz determined the structure of haemoglobin, the blood's oxygen carrier, sharing the 1962 Nobel Prize in Chemistry.
Sources
- Max Perutz American Crystallographic Association history
- Max Ferdinand Perutz (obituary by Francis Crick) Physics Today
- Max Perutz Wikipedia
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