The research groups headed by Prof. Christoph Dehio and Prof. Tilman Schirmer could demonstrate that through the alteration of one single amino acid this inhibition of enzyme activity can be relieved. Their findings, which have been published in the current issue of «Nature», will enable to investigate the physiological role of the potentially lethal function of Fic proteins in bacteria and higher organisms in the future.
Left: Binding of the antitoxin (blue) inhibits AMPylation of the target protein (magenta) by the Fic protein (grey), which allows normal bacterial growth. Right: In the absence of the antitoxin the target protein gets AMPylated, resulting in inhibition of cell division and thus abnormal filamentous growth of bacteria. Illustration: Universität Basel
Fic proteins are found in most forms of life ranging from simple bacteria to man. Only a few representatives of this protein family of about 3000 members have been investigated to date. These are enzymes that chemically alter other proteins through the attachment of an adenosine monophosphate group (AMP) derived from the important energy carrier ATP. This reaction, known as AMPylation, specifically modifies the function of the target proteins.
The biochemically best understood Fic proteins are produced by pathogenic bacteria and injected into host cells to alter cellular signaling proteins to the advantage of the bacterial intruder. However, the far majority of Fic proteins have probably evolved a function that is instrumental for the cell in which they are produced. Why the biochemical function of only a few of these Fic proteins has been elucidated so far was not clear. The reason has now been found by the collaborating research groups of the infection biologist Prof. Christoph Dehio and the structural biologist Prof. Tilman Schirmer.
The Active Center of Fic Proteins is BlockedThe scientists could show that an amino acid residue (glutamate-finger) protrudes into the active center of the Fic proteins. This prevents productive binding of ATP and explains the inactivate ground state of the enzyme. Surprisingly, in some Fic proteins the inhibiting residue is part of the Fic protein itself, whereas in other cases it is provided by a separate protein (called antitoxin). It was shown that upon truncation of the glutamate-finger by genetic manipulation or removal of the entire antitoxin the activity of the enzyme is awakened – sometimes with drastic consequences for the affected cells. Bacterial cells no longer divide, while human cells can even die.
Prof. Dr. Tilman Schirmer, Biozentrum, University of Basel, Tel. 061 267 28 89, Email: email@example.com
Heike Sacher | idw
Colorectal cancer: Increased life expectancy thanks to individualised therapies
20.02.2020 | Christian-Albrechts-Universität zu Kiel
Sweet beaks: What Galapagos finches and marine bacteria have in common
20.02.2020 | Max-Planck-Institut für Marine Mikrobiologie
The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.
Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...
Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.
Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...
Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices
The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...
Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.
Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.
After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.
"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.
12.02.2020 | Event News
16.01.2020 | Event News
15.01.2020 | Event News
21.02.2020 | Medical Engineering
21.02.2020 | Health and Medicine
21.02.2020 | Physics and Astronomy