Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Neutrons identify critical details in bacterial enzyme implicated in gastric cancer

02.02.2017

Neutron analysis at the Department of Energy's Oak Ridge National Laboratory is helping researchers better understand a key enzyme found in a bacterium known to cause stomach cancer.

Understanding the details of this enzyme, and thus the Helicobacter pylori bacteria's metabolism and biological pathways, could be central to developing drugs that act against H. pylori, but that do not attack the stomach's useful bacteria.


A nuclear density map of the bacterial enzyme HpMTAN's active site reveals the locations of the hydrogen atoms, including the unexpected observation of a hydrogen ion positioned midway between adenine and D198 residue.

Credit: ORNL

"Most drugs, including common antibiotics, use a generalized mechanism to bind to their targets, which, in turn, eliminates the good bacteria you need to stay healthy, as well as the bad bacteria," said Andrey Kovalevsky, one of the instrument scientists at the ORNL High Flux Isotope Reactor and coauthor of this research published in the Proceedings of the National Academy of Sciences.

"By understanding how this enzyme functions, we can get clues about how to fine-tune a drug to recognize only a specific target, which would eliminate some of the side effects that cause so many problems for people when a more generalized approach to kill bacteria is used."

Kovalevsky was part of a team led by Donald Ronning at the University of Toledo who used HFIR's IMAGINE instrument to study the metabolism of a bacterial enzyme known as H. pylori 5'-methylthioadenosine nucleosidase, or HpMTAN, which plays a key function in H. pylori. This bacterium garnered international attention in 2005 when a team of researchers was awarded the Nobel Prize in Medicine for determining its role as a "bacterial culprit" in the development of gastric conditions, including ulcers, chronic gastritis and cancer.

Ronning's team focused on H. pylori's use of a unique biosynthetic pathway to synthesize vitamin K2, which aids in the electron transfer processes, or chemical reactions, of all organisms. HpMTAN is one specific enzyme that functionbs within this unique pathway and provides the promising specific target or point of attack for new medications. Vitamin K2 acts to expedite the HpMTAN enzyme's interaction with other macromolecules, including the very bacterium that causes an array of gastric health issues.

Neutron crystallography at HFIR's IMAGINE instrument allowed researchers to accurately visualize the positions and predict the movements of hydrogen atoms in HpMTAN, especially those involved in the critical stages when the enzyme binds to its substrate and then proceeds with the catalytic reaction.

For a comprehensive view on the interatomic interactions, Ronning's team examined four different HpMTAN neutron structures to observe how ligands, or molecules that bind via noncovalent bonding, interacted with their respective enzyme sites.

"This knowledge will inform future drug design efforts by taking advantage of the known orientation of the nucleophilic water molecule and its intimate interactions with the neighboring components of the enzyme," Ronning said.

While Ronning qualified that the development of a new drug to treat gastric issues will take several years and continued study of the enzyme's behavior, he said that his team's research confirms HpMTAN's potential for use and this knowledge could, in fact, speed up the creation of such a medicine.

###

This research was partially funded through the National Institute of Health's National Institute of Allergy and Infectious Disease and a cooperative agreement with the National Aeronautics and Space Administration's Center for the Advancement of Science in Space. The work was conducted in part at the Heinz Maier-Leibnitz Research Neutron Source with the Technical University of Munich, both in Munich, Germany, and at ORNL's High Flux Isotope Reactor, a DOE Office of Science User Facility.

UT-Battelle manages ORNL for the DOE's Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit http://science.energy.gov/.

Media Contact

Katie Bethea
betheakl@ornl.gov
865-576-8039

 @ORNL

http://www.ornl.gov 

Katie Bethea | EurekAlert!

More articles from Health and Medicine:

nachricht Researchers image atomic structure of important immune regulator
11.12.2018 | Brigham and Women's Hospital

nachricht Potential seen for tailoring treatment for acute myeloid leukemia
10.12.2018 | University of Washington Health Sciences/UW Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

Im Focus: A bit of a stretch... material that thickens as it's pulled

Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.

Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...

Im Focus: The force of the vacuum

Scientists from the Theory Department of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science (CFEL) in Hamburg have shown through theoretical calculations and computer simulations that the force between electrons and lattice distortions in an atomically thin two-dimensional superconductor can be controlled with virtual photons. This could aid the development of new superconductors for energy-saving devices and many other technical applications.

The vacuum is not empty. It may sound like magic to laypeople but it has occupied physicists since the birth of quantum mechanics.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

 
Latest News

Some brain tumors may respond to immunotherapy, new study suggests

11.12.2018 | Studies and Analyses

Researchers image atomic structure of important immune regulator

11.12.2018 | Health and Medicine

Physicists edge closer to controlling chemical reactions

11.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>