June 2023 ESRFnews 15
SYNCHROTRON SERIAL CRYSTALLOGRAPHY
Jon Cartwright
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his group s last experiment, Martín García solved, for the first time, the 3D structure of NQO1, the human f lavoenzyme essential for the antioxidant defence system, bound to its substrate, NADH. It was, he says, a first step to understanding NQO1 s redox mechanism and its conformational dynamics, which his group will probe next. NQO1 is associated with a variety of diseases, including cancer, neurological disorders and cardio-
vascular diseases, he says. Viewing its dynamics will be critical to understanding its precise role in these.
Serial MX opens new doors for structural biology, although venturing out may require a culture shift on the part of users. The pipeline of traditional MX is geared around the growth of large crystals, whereas serial MX relies on many smaller crystals that can be suspended in media suitable for the various delivery methods. We re changing the paradigm, says de Sanctis. But ultimately, it will make the science easier. There is also the question of radiation damage, which has been explored in great depth for traditional cryogenic work but remains to be fully understood for room-temperature studies with the flux delivered at ID29 (see Does radiation damage warm samples? , left).
In the long term, de Sanctis believes traditional MX and serial MX will come to complement each other. For determining the structures of static molecules, traditional MX will probably be the fastest option. But for studying the dynamics of biological molecules in physiological conditions, serial MX is the way forward and many users are itching to check out this largely unexplored territory. You re always wondering, if you ve seen a molecule in two different states how did it get from A to B? says Tews. There s so much to learn about how the molecules themselves are driving things.
With the advent of time-resolved serial MX crystallography, we have the potential to revolutionise our understanding of life
Daniele de Sanctis (left) sets up an experiment for fixed-target serial MX with ID29 postdoc Julien Orlans.
