Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sulfurous ping-pong in the urinary tract

18.12.2008
Entirely new protein structures are very rarely found to drive known biochemical processes.

But molecular biologists from ETH Zurich have just succeeded in finding an example. They studied the protein ASST, present in pathogenic E. coli bacteria, which cause urinary tract infections. In addition to an entirely new structure, the researchers found a transfer mechanism similar to ping-pong, whereby the "ball" is held a previously unknown manner.

Transfer of information is a basic property of biological systems. Common examples include transfer of genetic information or nerve impulses. Transmission of signals occurs at an even more fundamental level between and within cells, including signaling molecules, which bear a phosphate or a sulfate group. The latter contain a sulfur atom. Since these processes are of supreme importance, they have been extensively studied and a number of mechanisms and related protein structures have been revealed.

Thus, it is even more surprising that ETH Zurich researchers studying transfer processes among sulfurylated molecules discovered a protein, sulfotransferase, whose function is known but which exhibits a previously unknown structure. The group of Rudi Glockshuber recently published a paper about the protein, called ASST, in the scientific journal PNAS.

ETH Zurich researchers crossed the disulfide bridge

The discovery of the signal transfer mechanism happened accidentally, as is often the case in scientific research. The Glockshuber group studies protein folding mechanisms, where bonds between two sulfur atoms in a protein chain, disulfide bridges, play an important role. While examining gene data banks, the researchers stumbled upon an unusual gene combination present in strains of E. coli which cause urinary tract infections: two genes for the disulfide bond formation machinery were clustered with the gene for ASST. Since bacteria often contain functionally-related genes close to each other, the researchers decided to use ASST to study disulfide bond formation.

Hence, they decided to elucidate the structure of ASST. This turned out to be a tantalizing task because this protein is large and present in only minute amounts in a bacterial compartment called periplasm. By growing large-scale bacterial cultures the scientists could obtain sufficient material for crystallographic studies. The crystals of ASST were analyzed at the Swiss Light Source at Paul Scherrer Institut in Villigen.

Two propellers building a cage

This analysis, down to 2 Ångström resolution, revealed that ASST indeed contains an extremely short disulfide bond which can presumably only be formed by the action of the disulfide bond formation machinery genetically associated with ASST. This disulfide bridge is a prerequisite for proper folding of this protein and could also play a role in regulating its catalytic activity. However, these features were almost outweighed by other unusual discoveries: the researchers found a previously never-observed protein structure to catalyze this process. This structure consists of two equal propeller-like parts which contain active sites in the center of the two propellers, built of beta-pleated sheets. Such a structure has never been observed for a sulfotransferase.

How does this two-propeller machine function? To answer this question, the scientists replaced individual amino acids, i.e. building blocks of the protein. In addition, they used molecules acting as sulfuryl-donors and repeated crystallographic analyses. Now they saw that five amino acids containing nitrogen are essential for the function of ASST. They built a reaction cage that accommodates both the donor and the acceptor of the sulfuryl group. Furthermore, during the transfer, the sulfuryl group is directly, covalently bound to a histidine side chain of ASST. Thus, the signal is first transferred from the donor to ASST and subsequently from ASST to the acceptor. Such a ping-pong mechanism is unique in the processes of sulfuryl transfer.

Point of vantage against the "bad" E. coli strains

A new structure, a new mechanism - this opens up medically relevant perspectives. Goran Malojcic; the first author of this study, explains several interesting points. Since ASST is not present in mammals, the protein could be a feasible target for antibacterial drugs. Furthermore, since ASST is present exclusively in E. coli strains causing urinary tract infections, a selective action against these bacteria would leave the other, useful bacteria intact.

In addition, Malojcic intends to collaborate with in-silico chemists, who use computers to design molecules, and develop inhibitors of ASST. He also plans to use ASST for the synthesis of novel molecules bearing sulfuryl groups.

Renata Cosby | idw
Further information:
http://www.ethz.ch

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

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...

Im Focus: Tracing down linear ubiquitination

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...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

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...

Im Focus: Researchers Imitate Molecular Crowding in Cells

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

NASA examines Peru's deadly rainfall

24.03.2017 | Earth Sciences

What does congenital Zika syndrome look like?

24.03.2017 | Health and Medicine

Steep rise of the Bernese Alps

24.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>