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
When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie
WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
23.03.2017 | Life Sciences
23.03.2017 | Power and Electrical Engineering
23.03.2017 | Earth Sciences