At last the team had a crystal; next stop, the synchrotron. At Diamond, they could use X-rays on the protein crystallography beamlines to work out the 3D structure of TB’s waxy coat enzyme – with this they hoped to understand how the enzyme worked and block its action; but it wasn’t that simple. “Everything that could have gone wrong with this little crystal did go wrong”, says Elspeth. When the sample went under the Diamond microscope it gave a good image, as they had hoped, but the structure was not nearly as clear as it should have been. The symmetry didn’t look right and some features weren’t clear enough. It was then that Ed Lowe in the team realised that they needed another round of experiments to get the information. Ed recalls: “It was a mystery why the structure was so poor quality. We needed more data but the tiny crystal was already radiation damaged so we knew our second attempt was going to give poorer results. It was an anxious time.”
The team had no choice: they had to run the experiment again; but their single crystal had been damaged after being exposed to Diamond’s synchrotron light. Faced with the daunting prospect of trying to grow another crystal, the group tried again with the damaged sample. This final push proved vital. After many years and much toil, the team finally had the structure of the coveted enzyme.
Project leader Edith Sim reflects on all of the work that went into the findings: “The extra data this experiment yielded made it possible to find the true symmetry and a much clearer structure. This satisfying conclusion which gives the structure of a potential target for TB treatment is the culmination of studies at Diamond, with the earliest studies being carried out over a decade ago by many people including Diamond’s James Sandy.”
The story of this team’s fight against TB is emblematic of the struggle scientists often go through as they try to advance their research. Discoveries such as this are not arbitrary; they’re the culmination of months and years of effort, and each step forward results from untold hours of work, emotional turmoil, and determination. So the next time you hear a cry of ‘Eureka!’, think of the people behind that discovery, for all of science is a story of human endeavour.