Features | Partner Sites | Information | LinkXpress
Sign In
JIB
BioConferenceLive
GLOBETECH PUBLISHING

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



comments powered by Disqus

Channels

Drug Discovery

view channel
Image: Molecular rendering of the crystal structure of parkin (Photo courtesy of Wikimedia Commons).

Cinnamon Feeding Blocks Development of Parkinson's Disease in Mouse Model

A team of neurological researchers has identified a molecular mechanism by which cinnamon acts to protect neurons from damage caused by Parkinson's disease (PD) in a mouse model of the syndrome.... Read more

Therapeutics

view channel
Image: This type of electronic pacemaker could become obsolete if induction of biological pacemaker cells by gene therapy proves successful (Photo courtesy of Wikimedia Commons).

Gene Therapy Induces Functional Pacemaker Cells in Pig Heart Failure Model

Cardiovascular disease researchers working with a porcine heart failure model have demonstrated the practicality of using gene therapy to replace implanted electronic pacemakers to regulate heartbeat.... Read more

Lab Technologies

view channel
Image: A one-year-old baby sits in a brain scanner, called magnetoencephalography (MEG)—a noninvasive approach to measuring brain activity. The baby listens to speech sounds such as “da” and “ta” played over headphones while researchers record her brain responses (Photo courtesy of the Institute for Learning & Brain Sciences at the University of Washington).

Brain Scanner Shows Infants’ Brains Rehearse Speech Sounds Months Before Their First Words

New research in 7- and 11-month-old infants revealed that speech sounds stimulate brain regions that coordinate and plan motor movements for speech. The new study suggests that babies’ brains begin establishing... Read more

Business

view channel

Cancer Immunotherapy Sector Predicted to Surge to USD 9 Billion Across Major Pharma Through 2022

The immunotherapy market will experience substantial growth through 2022, increasing from USD 1.1 billion in 2012 to nearly USD 9 billion in 2022 (corresponding to 23.8% annual growth) in the United Kingdom, United States, France, Germany, Italy, Spain, and Japan, according to recent market research. This notable growth... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.