In This Issue... March 21, 2013

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Cool Image: Nanoparticles and Lung Function

Prajnaparamita Dhar • University of Kansas

This image may resemble a trendy textile from a fashion designer’s spring collection, but it’s actually a microscopic image of lung surfactant, a lipid-protein material that aids in respiration by reducing the amount of energy needed. Using microscopy techniques, the researchers captured a snapshot of the changes that occur (black) when surfactant molecules are stressed by carbon nanoparticles. The scientists found that if inhaled, carbon nanoparticles could influence the function of the main lipid component of surfactant. A likely gateway for nanoparticles to enter the body is through the lungs, so this and future studies may help scientists improve drug delivery methods. Read more…

Structural Details of Enzyme Involved in Antibiotic Resistance

Andrzej Joachimiak • Argonne National Laboratory
James Sacchettini • Texas A&M University

Disease-causing bacteria like E. coli have a natural defense against antibiotics—an enzyme called NDM-1. Researchers now have a more detailed understanding of how the enzyme works. NDM-1 binds to and breaks the ß-lactam ring, a structure that antibiotics need to function. Certain metals, including zinc, manganese and cadmium, can bind to the enzyme’s active site and to the ß-lactam ring. While some metals allow the enzyme to cleave the ring, cadmium tends to prevent it from doing so. This inhibitor may offer clues to designing more effective antibiotics, especially ones for drug-resistant “superbugs.”
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Caption: NDM-1 is present in a number of pathogenic bacteria, including Klebsiella pneumoniae, which are often the cause of hospital-acquired infections involving the urinary and pulmonary systems. Credit: CDC. High res. image (JPG, 69KB)

New Catalysts Improve Production of Important Organic Molecules

Amir Hoveyda • Boston College

Making molecules for biomedical uses is tricky. The work is often expensive and time-consuming, requiring extreme temperatures, toxic ingredients and rare or precious metals. Now, chemists synthesizing common organic molecules can overcome these challenges by employing a new class of catalysts (substances used to spur chemical reactions). The catalysts are renewable, cheap to prepare and easy to use. They promote extraordinarily selective reactions that favor desired products over chemically similar but inactive molecules. The catalysts will enable chemists to create a wide variety of biologically and medically useful molecules in a sustainable, economical, reliable and environmentally friendly way. Read more...

Caption: Newly discovered chemical catalysts make it easier, cheaper and “greener” to synthesize many useful organic molecules, including this one with anticancer properties. High res. image (JPG, 64KB)

A Potential Cure for Kissing Bug’s Infectious Bite

Galina Lepesheva and Jeffrey Johnston • Vanderbilt University
Fernando Villalta • Meharry Medical College

Chagas disease, which is caused by a parasite and transmitted by a “kissing bug,” can lead to intestinal infection, heart disease and even death. Right now, treatment options are limited and toxic. This might change if new research on VNI, a small molecule, continues to show promise. In mouse models, researchers used VNI to inhibit an enzyme that the parasite needs to survive, achieving both a 100 percent parasitological cure and survival rate with no toxic side effects. Read more...

This work also was supported by NIH’s National Institute of Allergy and Infectious Diseases and National Institute on Minority Health and Health Disparities.

Caption: Kissing bugs transmit the parasite, Trypanosoma cruzi. Credit: CDC. High res. image (JPG, 57KB)

First Step-by-Step Snapshots of Transcription Initiation

Eva Nogales • Lawrence Berkeley National Laboratory

When a gene is turned on—such as insulin in pancreatic cells or melanin in skin cells—an enzyme called RNA polymerase transcribes the genetic information from DNA into RNA. But RNA polymerase can’t initiate the process alone. A bevy of helper molecules identify the gene’s start site, provide a landing pad for the polymerase and prime the DNA for transcription. These helpers alight onto the DNA and assemble into a growing complex in a precise, stepwise manner that has now been captured in a series of detailed molecular snapshots. Knowing how this intricate complex forms provides a valuable framework for understanding malfunctions that cause cancer and other medical problems. Read more...

This work also was supported by NIH’s National Cancer Institute.

Caption: The first step-by-step snapshots of the assembly of transcription factors and RNA polymerase in preparation for transcription initiation. Credit: Eva Nogales, Lawrence Berkeley National Laboratory. High res. image (JPG, 37KB)