Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
PURITAN MEDICAL
GLOBETECH PUBLISHING LLC

Researchers Describe Novel Methods for Disabling Bacterial Proteases

By BiotechDaily International staff writers
Posted on 27 Feb 2014
Image: The target: bacterial protease ClpP (Photo courtesy of Technische Universitaet Muenchen).
Image: The target: bacterial protease ClpP (Photo courtesy of Technische Universitaet Muenchen).
Image: Several small molecules are able to split the protease ClpP into inactive smaller units, which massively disturbs the bacterial metabolism ClpP (Photo courtesy of Technische Universitaet Muenchen).
Image: Several small molecules are able to split the protease ClpP into inactive smaller units, which massively disturbs the bacterial metabolism ClpP (Photo courtesy of Technische Universitaet Muenchen).
A paper described previously unrecognized mechanisms that can be used to permanently deactivate critical bacteriological proteases.

Proteases are responsible for the pathogenic effects of many kinds of bacteria, and considerable research effort is involved in developing effective ways of inhibiting their action.

Investigators at the Technische Universitaet Muenchen (Munich, Germany) recently described novel approaches for silencing the activity of bacterial ClpP protease. In the January 29, 2014, issue of the Journal of the American Chemical Society they presented a novel mechanism of protease inhibition that relied on active-site-directed small molecules that disassembled the protease complex. They showed the applicability of this mechanism within the ClpP protease family, whose members are tetradecameric serine proteases and serve as regulators of several cellular processes, including homeostasis and virulence.

In addition, they reported the selective beta-sultam-induced dehydroalanine formation of the active site serine. This reaction proceeded through sulfonylation and subsequent elimination, thereby obliterating the catalytic charge relay system. The identity of the dehydroalanine was confirmed by mass spectrometry and crystallography. Activity-based protein profiling experiments suggested the formation of a dehydroalanine moiety in living Staphylococcus aureus cells upon beta-sultam treatment.

The mechanisms described here point towards the possibility of developing protease inhibitors that do not rely on complete blocking of the enzymes' catalytic or binding sites.

“ClpP inhibitors used in the past have one decisive disadvantage,” said senior author Dr. Stephan Sieber, professor of organic chemistry at the Technische Universitaet Muenchen. “They do not permanently disarm the proteins, but only work for a few hours. On top of that, to be effective they must attack all active centers of the protein.”

Related Links:

Technische Universitaet Muenchen



Channels

Drug Discovery

view channel
Image: The microneedle patch can dissolve in the skin, delivering the flu vaccine painlessly (Photo courtesy of Dr. Shinsaku Nakagawa, Osaka University).

Japanese Researchers Demonstrate Novel Transcutaneous Influenza Vaccination Using a Dissolving Microneedle Patch

Vaccination via a biodegradable microneedle patch was shown to generate immune response to various strains of the influenza virus that were equal to or stronger than those induced by traditional hypodermic... Read more

Lab Technologies

view channel
Image: The Leica DM2500 LED Microscope for clinical laboratories and research applications (Photo courtesy of Leica Microsystems).

New LED Microscope Completes Line of Clinical and Research Tools

A popular microscope used for both clinical and research applications is now available with LED illumination. The Leica (Wetzlar, Germany) DM2500 and DM2500 LED microscopes represent a class of tools... Read more

Business

view channel

Partners to Seek Novel Drugs to Treat Fibrotic Diseases

A global biopharmaceutical company and an American university hospital-based research institute have agreed to collaborate on the diagnosis and cure of fibrotic diseases. Fibrotic diseases such as scleroderma, renal fibrosis, and idiopathic pulmonary fibrosis are characterized by the gradual formation of excess fibrous... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.