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Neutrons Provide New Approach for Medications to Combat Helicobacter pylori

20 January 2017

Fifty percent of the world’s population harbours this bacterium in their stomach: Helicobacter pylori (H. pylori). This infection, which also occurs commonly in Germany, can trigger illnesses such as gastritis or stomach cancer. Now an international research team has used neutrons to explain the functionality of an important enzyme in the pathogen’s metabolism. This could serve as a viable target for new medications.

MTANPlacing a crystal of the enzyme MTAN in the center of the neutron beam at the instrument BIODIFF
Copyright: Andreas Ostermann / TUM

Scientists from the University of Toledo (USA), the Victoria University of Wellington (New Zealand), the Heinz Maier-Leibnitz neutron research facility at the TU Munich, the Jülich Centre for Neutron Science (JCNS) and Oak Ridge National Laboratory (ORNL, USA) have studied different variations of the enzyme 5'-methylthioadenosine nucleosidase (MTAN) and could thus determine an accurate picture of how it operates. To do so, they used both the neutron diffractometer BioDiff, operated jointly by Forschungszentrum Jülich and the TU Munich at the Heinz Maier-Leibnitz Zentrum in Garching, along with the neutron source at the ORNL. The scientists chose to look at MTAN, as this enzyme is a promising candidate for the development of drugs which only have an effect on H. pylori. Unlike humans and many useful bacteria, this species uses MTAN to synthesize vitamin K2.

MTAN-B-Diffraction-imageDiffraction image resulting from neutron scattering at the instrument BIODIFF
Copyright: Andreas Ostermann / TUM

In an important step in the synthesis of vitamin K2, MTAN binds itself with a precursor of the vitamin using hydrogen bonds in order to detach a side chain. The important positions and position changes of the hydrogen atoms in this process were however until now not known with any certainty. The usual method of determining the structure of an enzyme, i.e. crystal structure analysis using x-ray radiation, is of limited help in this case, since x-ray radiation is virtually blind to hydrogen atoms. Therefore the researchers used neutrons to determine the enzyme’s structure, as they are particularly sensitive to hydrogen atoms. “One of the disadvantages of using neutrons to determine a protein structure is that particularly large protein crystals have to be produced,” explained Dr. Tobias Schrader from JCNS who, together with Dr. Andreas Ostermann from the TUM, operates the instrument. “However, as the current study shows, the effort was certainly worthwhile.”

Original publication:

Michael T. Banco, Vidhi Mishra, Andreas Ostermann, Tobias E. Schrader, Gary B. Evans, Andrey Kovalevsky, and Donald R. Ronning
Neutron structures of the Helicobacter pylori 5'-methylthioadenosine nucleosidase highlight proton sharing and protonation states.
PNAS, November 16, 2016, DOI:10.1073/pnas.1609718113

Further information:

Jülich Centre for Neutron Science (JCNS)

Heinz Maier-Leibnitz Zentrum

Press release from TU Munich from 20.12.2016, “Neutrons help to determine enzyme function”  


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