We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
INTEGRA BIOSCIENCES AG

Download Mobile App




Researchers Describe Novel Methods for Disabling Bacterial Proteases

By LabMedica International staff writers
Posted on 27 Feb 2014
Print article
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


Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
Specimen Collection & Transport
POCT Fluorescent Immunoassay Analyzer
FIA Go
Gold Member
Real-time PCR System
GentierX3 Series

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: MOF materials efficiently enrich cfDNA and cfRNA in blood through simple operational process (Photo courtesy of Science China Press)

Blood Circulating Nucleic Acid Enrichment Technique Enables Non-Invasive Liver Cancer Diagnosis

The ability to diagnose diseases early can significantly enhance the effectiveness of clinical treatments and improve survival rates. One promising approach for non-invasive early diagnosis is the use... Read more

Hematology

view channel
Image: The low-cost portable device rapidly identifies chemotherapy patients at risk of sepsis (Photo courtesy of 52North Health)

POC Finger-Prick Blood Test Determines Risk of Neutropenic Sepsis in Patients Undergoing Chemotherapy

Neutropenia, a decrease in neutrophils (a type of white blood cell crucial for fighting infections), is a frequent side effect of certain cancer treatments. This condition elevates the risk of infections,... Read more

Pathology

view channel
Image: The OvaCis Rapid Test discriminates benign from malignant epithelial ovarian cysts (Photo courtesy of INEX)

Intra-Operative POC Device Distinguishes Between Benign and Malignant Ovarian Cysts within 15 Minutes

Ovarian cysts represent a significant health issue for women globally, with up to 10% experiencing this condition at some point in their lives. These cysts form when fluid collects within a thin membrane... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.