Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Events

06 Jun 2016 - 09 Jun 2016
22 Jun 2016 - 24 Jun 2016
04 Jul 2016 - 06 Jul 2016

European Collaborators Define Dermcidin's Mode of Action

By BiotechDaily International staff writers
Posted on 06 Mar 2013
Print article
A team of European molecular biologists have published the crystal structure and functional mechanism of the human antimicrobial peptide dermcidin.

Dermcidin (DCD) is a human antimicrobial peptide (AMP) that is constitutively expressed in sweat glands and secreted into sweat. By postsecretory proteolytic processing in human sweat, the precursor protein gives rise to several short DCD peptides varying in length from 25 to 48 amino acids and with net charges between minus two and plus two. Several DCD peptides show antimicrobial activity against pathogenic microorganisms such as Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Candida albicans, Staphylococcus epidermidis, Pseudomonas putida, and methicillin-resistant S. aureus as well as rifampin- and isoniazid-resistant Mycobacterium tuberculosis. DCD-derived peptides are active under high-salt conditions and in a buffer resembling human sweat. These peptides have diverse and overlapping spectra of activity that are independent of the net peptide charge, and previous studies showed that DCD peptides interacted with the bacterial cell envelope and killed gram-negative bacteria without forming pores in membranes.

Investigators at the University of Edinburgh (United Kingdom), the Max Planck Institute for Biophysical Chemistry (Goettingen, Germany), the Max Planck Institute for Developmental Biology (Tübingen, Germany), and the University of Strasbourg (France) collaborated in the effort to define the mode of action of DCD at the molecular and atomic levels.

In the February 20, 2013, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) they presented the X-ray crystal structure as well as solid-state NMR spectroscopy, electrophysiology, and molecular dynamic simulations of this major human antimicrobial.

The results demonstrated that dermcidin formed an architecture of high-conductance transmembrane channels, composed of zinc-connected trimers of antiparallel helix pairs. Molecular dynamics simulations elucidated the unusual membrane permeation pathway for ions and showed adjustment of the pore to various membranes. Water and charged particles were able to flow uncontrollably across the membrane, eventually killing harmful microbes.

The authors predicted that their findings may form a foundation for the structure-based design of a new generation of peptide antibiotics.

Related Links:
University of Edinburgh
Max Planck Institute for Biophysical Chemistry
Max Planck Institute for Developmental Biology



Print article

Channels

Drug Discovery

view channel

Experimental Small-Molecule Anticancer Drug Blocks RAS-binding Domains

The experimental small-molecule anticancer drug rigosertib was shown to block tumor growth by acting as an RAS-mimetic and interacting with the RAS binding domains of RAF kinases, resulting in their inability to bind to RAS, which inhibited the RAS-RAF-MEK pathway. Oncogenic activation of RAS genes due to point mutations... Read more

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Lab Technologies

view channel

Huge Modifiable Biomedical Database to Be Available on the Wikidata Site

Genome researchers are exploiting the power of the open Internet community Wikipedia database to create a comprehensive resource for geneticists, molecular biologists, and other interested life scientists. While efficiency in generating scientific data improves almost daily, applying meaningful relationships between... Read more

Business

view channel

European Biotech Agreement to Promote Antigen-Drug Conjugation Technology

Two European biotech companies have joined forces to exploit and commercialize an innovative, site-specific ADC (antigen-drug conjugate) conjugation technology. ProBioGen (Berlin, Germany), a company specializing in the development and manufacture of complex glycoproteins and Eucodis Bioscience (Vienna, Austria), a... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.