The 6th Dorothy Hodgkin memorial lecture

"A Piece in the Jigsaw: G6PD - The protein behind an hereditary disease"
presented by Dr. Margaret Adams, Somerville College
and Laboratory of Molecular Biophysics, University of Oxford
in the University Museum, Oxford at 5pm on 9 March 2004

Dr Margaret Adams was a research student of Dorothy Hodgkin and has continued to work in the field of protein crystallography. She is the Dorothy Hodgkin and E.P. Abraham Fellow of Somerville College and was the supervisor of Dr Claire Naylor who gave last year's lecture. This lecture was organised by the Oxford International Women's Festival with the support of Oxford AWiSE and Somerville College. (The founding of this lecture series was described in 'Crystallography News' no. 85 June 2003 p18)

Dr Adams began her talk by giving a brief overview of how x-ray crystallography works. She described the work of Dorothy Hodgkin who was awarded the Nobel Prize forty years ago this year. Dorothy established the crystal structures of penicillin, insulin and vitamin B12, among many others, and Dr Adams showed illustrations of early diagrams and models of these proteins. She described an incident where Dorothy had established the three dimensional structure of a protein after studying it's diffraction patterns for about an hour, when research students had been struggling over them for days. She explained that advances in the technology and the storage capability of computers now enabled those without Dorothy's insight to solve structures in a fraction of the time that it had taken forty years ago.

Dr Adams own research is concerned with the enzyme glucose-6-phosphate dehydrogenase (G6PD) which is an essential protein in the metabolic pathway, involved in combating oxidative stress. People having a G6PD deficiency can experience neo-natal jaundice and haemolytic anaemia, which is chronic for some severe deficiencies, intolerance to fava beans (favism) or to drugs such as aspirin and anti-malarials. The latter is a particular problem as this deficiency is prevalent in areas where malaria is endemic, although the deficiency does confer some protection against malaria. The deficiency is a genetic disorder affecting 400 million people worldwide. The protein is coded for on the X chromosome, and so men are far more likely to suffer from the deficiency, although it has been found in some women unfortunate enough to have an abnormality in both X chromosomes.

Dr Adams showed how her studies of the crystal structure of G6PD had revealed how small changes in the make-up of the protein can lead to changes in it's three dimensional structure and stability and thus affect it's efficiency of action. She concluded with some quotes from classical literature about Pythagoras who had a profound fear of beans, which she suggested may have been due to an awareness of favism so many centuries ago.

Dr Carolyn Carr
Cardiac Metabolism Research Group
University of Oxford


Note: This report was first distributed by email to members of the Oxford area AWISE, the Association of Women in Science and Engineering. We are grateful to Dr. Carr for permission to republish it in 'Crystallography News'. Click on the BCA website at URL: http://bca.cryst.bbk.ac.uk/bca/CNews/2003/Jun03/DHmem.htm for a page of links to the websites of the lecture sponsors.