Towards prevention of diabetes linked substance produced by human gut microbiota 

The team at the Novo Nordisk Foundation funded life science beamline MicroMAX welcomed the first users in December 2023. In the experiment the users investigated an enzyme that may be found in some bacteria of human gut microbiota and may have a role in the development of diabetes and other diseases.

An enzyme called urocanate reductase may be present in the bacteria that are found in the human gut. The enzyme breaks down urocanic acid, a natural constituent of skin and other tissues of the body, into the metabolite imidazole propionate. The metabolite has been linked to diabetes and other diseases.

The user team from Lund University used MicroMAX to investigate the molecular structure of the enzyme.

“A possible therapeutic strategy is to inhibit the enzyme and prevent the imidazole propionate production. The high-resolution atomic structure is needed to design inhibitor molecules that could occupy the active site of the enzyme,” says Raminta Venskutonyte, one of the researchers who conducted the study.

The experiment was conducted using X-ray diffraction at room temperature on a crystal prepared from a purified enzyme. One of the features of MicroMAX is that the experimental setup can handle even small amounts of samples, so-called microcrystals. It is important as it lets the researchers study samples that cannot be made to form large crystals and extend investigations into new areas.

“We aim to carry out time-resolved studies using microcrystals of urocanate reductase to further clarify its enzymatic mechanism. We are also looking forward to using MicroMAX in other projects involving medically interesting proteins, which only yield microcrystals,” concludes Raminta Venskutonyte.

Read more om the MAX IV website

Image: Raminta Venskutonyte in the experiment hutch at beamline MicroMAX

Advancing materials science with the help of biology and a dash of dish soap

High-speed X-ray free-electron lasers have unlocked the crystal structures of small molecules relevant to chemistry and materials science, proving a new method that could advance semiconductor and solar cell development.

Compounds that form tiny crystals hold secrets that could advance renewable energy generation and semiconductor development. Revealing the arrangement of their atoms has already allowed for breakthroughs in materials science and solar cells. However, existing techniques for determining these structures can damage sensitive microcrystals.

Now scientists have a new tool in their tool belts: a system for investigating microcrystals by the thousands with ultrafast pulses from an X-ray free-electron laser (XFEL), which can collect structural information before damage sets in. This approach, developed over the past decade to study proteins and other large biological molecules at the Department of Energy’s SLAC National Accelerator Laboratory, has now been applied for the first time to small molecules that are of interest to chemistry and materials science.

Researchers from the University of Connecticut, SLAC, DOE’s Lawrence Berkeley National Laboratory and other institutions developed the new process, called small molecule serial femtosecond X-ray crystallography or smSFX, to determine the structures of three compounds that form microcrystal powders, including two that were previously unknown. The experiments took place at SLAC’s Linac Coherent Light Source (LCLS) XFEL and the SACLA XFEL in Japan.

Read more on the SLAC website

Image: Artist’s rendition of the X-ray beam illuminating a solution of powdered metal-organic materials called chalcogenolates.

Credit: Ella Maru Studios