Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

European Collaborators Define Dermcidin's Mode of Action

By BiotechDaily International staff writers
Posted on 06 Mar 2013
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



Channels

Drug Discovery

view channel
Image: Molecular model of the protein Saposin C (Photo courtesy of Wikimedia Commons).

Nanovesicles Kill Human Lung Cancer Cells in Culture and in a Mouse Xenograft Model

Nanovesicles assembled from the protein Saposin C (SapC) and the phospholipid dioleoylphosphatidylserine (DOPS) were shown to be potent inhibitors of lung cancer cells in culture and in a mouse xenograft model.... Read more

Biochemistry

view channel

Possible New Target Found for Treating Brain Inflammation

Scientists have identified an enzyme that produces a class of inflammatory lipid molecules in the brain. Abnormally high levels of these molecules appear to cause a rare inherited eurodegenerative disorder, and that disorder now may be treatable if researchers can develop suitable drug candidates that suppress this enzyme.... Read more

Lab Technologies

view channel
Image: The FLUOVIEW FVMPE-RS Gantry microscope (Photo courtesy of Olympus).

New Multiphoton Laser Scanning Microscope Configurations Expand Research Potential

Two new configurations of a state-of-the-art multiphoton laser scanning microscope extend the usefulness of the instrument for examining rapidly occurring biological events and for obtaining images from... Read more

Business

view channel

Roche Acquires Signature Diagnostics to Advance Translational Research

Roche (Basel, Switzerland) will advance translational research for next generation sequencing (NGS) diagnostics by leveraging the unique expertise of Signature Diagnostics AG (Potsdam, Germany) in biobanks and development of novel NGS diagnostic assays. Signature Diagnostics is a privately held translational oncology... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.