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
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine