PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

DNA nanotechnology places enzyme catalysis within an arm's length

DNA nanotechnology places enzyme catalysis within an arm's length
2014-05-25
(Press-News.org) VIDEO: In the middle of a DNA scaffold is affixed a single strand of DNA, with NAD+ tethered to the end like a ball and string. ASU Professor Han Yan refers...
Click here for more information.

Using molecules of DNA like an architectural scaffold, Arizona State University scientists, in collaboration with colleagues at the University of Michigan, have developed a 3-D artificial enzyme cascade that mimics an important biochemical pathway that could prove important for future biomedical and energy applications.

The findings were published in the journal Nature Nanotechnology. Led by ASU Professor Hao Yan, the research team included ASU Biodesign Institute researchers Jinglin Fu, Yuhe Yang, Minghui Liu, Professor Yan Liu and Professor Neal Woodbury along with colleagues Professor Nils Walter and postdoctoral fellow Alexander Johnson-Buck at the University of Michigan.

Researchers in the field of DNA nanotechnology, taking advantage of the binding properties of the chemical building blocks of DNA, twist and self-assemble DNA into ever-more imaginative 2- and 3-dimensional structures for medical, electronic and energy applications.

In the latest breakthrough, the research team took up the challenge of mimicking enzymes outside the friendly confines of the cell. These enzymes speed up chemical reactions, used in our bodies for the digestion of food into sugars and energy during human metabolism, for example.

"We look to Nature for inspiration to build man-made molecular systems that mimic the sophisticated nanoscale machineries developed in living biological systems, and we rationally design molecular nanoscaffolds to achieve biomimicry at the molecular level," Yan said, who holds the Milton Glick Chair in the ASU Department of Chemistry and Biochemistry and directs the Center for Molecular Design and Biomimicry at the Biodesign Institute.

With enzymes, all moving parts must be tightly controlled and coordinated, otherwise the reaction will not work. The moving parts, which include molecules such as substrates and cofactors, all fit into a complex enzyme pocket just like a baseball into a glove. Once all the chemical parts have found their place in the pocket, the energetics that control the reaction become favorable, and swiftly make chemistry happen. Each enzyme releases its product, like a baton handed off in a relay race, to another enzyme to carry out the next step in a biochemical pathway in the human body.

For the new study, the researchers chose a pair of universal enzymes, glucose-6 phosphate dehydrogenase (G6pDH) and malate dehydrogenase (MDH), that are important for biosynthesis—making the amino acids, fats and nucleic acids essential for all life. For example, defects found in the pathway cause anemia in humans. "Dehydrogenase enzymes are particularly important since they supply most of the energy of a cell", said Walter. "Work with these enzymes could lead to future applications in green energy production such as fuel cells using biomaterials for fuel."

In the pathway, G6pDH uses the glucose sugar substrate and a cofactor called NAD to strip hydrogen atoms from glucose and transfer to the next enzyme, MDH, to go on and make malic acid and generate NADH in the process, which is used for as a key cofactor for biosynthesis.

Remaking this enzyme pair in the test tube and having it work outside the cell is a big challenge for DNA nanotechnology.

To meet the challenge, they first made a DNA scaffold that looks like several paper towel rolls glued together. Using a computer program, they were able to customize the chemical building blocks of the DNA sequence so that the scaffold would self-assemble. Next, the two enzymes were attached to the ends of the DNA tubes.

In the middle of the DNA scaffold, they affixed a single strand of DNA, with the NAD+ tethered to the end like a ball and string. Yan refers to this as a swinging arm, which is long, flexible and dexterous enough to rock back and forth between the enzymes.

Once the system was made in a test tube by heating up and cooling the DNA, which leads to self-assembly, the enzyme parts were added in. They confirmed the structure using a high-powered microscope, called an AFM, which can see down to the nanoscale, 1,000 times smaller than the width of a human hair.

Like architects, the scientists first built a full-scale model so they could test and measure the spatial geometry and structures, including in their setup a tiny fluorescent dye attached to the swinging arm. If the reaction takes place, they can measure a red beacon signal that the dye gives off---but in this case, unlike a traffic signal, a red light means the reaction works.

Next, they tried the enzyme system and found that it worked just the same as a cellular enzyme cascade. They also measured the effect when varying the distance between the swinging arm and the enzymes. They found there was a sweet spot, at 7nm, where the arm angle was parallel to the enzyme pair.

With a single swinging arm in the test tube system working just like the cellular enzymes, they decided to add arms, testing the limits of the system with up to 4 added arms. They were able to show that as each arm was added, the G6pDH could keep up to make even more product, while the MDH had maxed out after only two swinging arms. "Lining enzymes up along a designed assembly line like Henry Ford did for auto parts is particularly satisfying for someone living near the motor city Detroit," said Walter.

The work also opens a bright future where biochemical pathways can be replicated outside the cell to develop biomedical applications such as detection methods for diagnostic platforms.

"An even loftier and more valuable goal is to engineer highly programmed cascading enzyme pathways on DNA nanostructure platforms with control of input and output sequences. Achieving this goal would not only allow researchers to mimic the elegant enzyme cascades found in nature and attempt to understand their underlying mechanisms of action, but would facilitate the construction of artificial cascades that do not exist in nature," said Yan.

INFORMATION: The research is supported by a Multi-disciplinary University Research Initiative (MURI) grant from Army Research Office, with the goal of translating biochemical pathways into non-cellular environments.

[Attachments] See images for this press release:
DNA nanotechnology places enzyme catalysis within an arm's length DNA nanotechnology places enzyme catalysis within an arm's length 2 DNA nanotechnology places enzyme catalysis within an arm's length 3

ELSE PRESS RELEASES FROM THIS DATE:

Gene mutation found for aggressive form of pancreatic cancer

2014-05-25
Researchers at the University of California, San Diego School of Medicine have identified a mutated gene common to adenosquamous carcinoma (ASC) tumors – the first known unique molecular signature for this rare, but particularly virulent, form of pancreatic cancer. The findings are published in the May 25 advance online issue of Nature Medicine. Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, with roughly 45,220 new cases diagnosed and more than 38,400 deaths annually. Both numbers are rising. ASC cases are infrequent, but ...

Mice with 'mohawks' help scientists link autism to 2 biological pathways in brain

2014-05-25
"Aha" moments are rare in medical research, scientists say. As rare, they add, as finding mice with Mohawk-like hairstyles. But both events happened in a lab at NYU Langone Medical Center, months after an international team of neuroscientists bred hundreds of mice with a suspect genetic mutation tied to autism spectrum disorders. Almost all the grown mice, the NYU Langone team observed, had sideways,"overgroomed" hair with a highly stylized center hairline between their ears and hardly a tuft elsewhere. Mice typically groom each other's hair. Researchers say they ...

Buried fossil soils found to be awash in carbon

Buried fossil soils found to be awash in carbon
2014-05-25
MADISON, Wis. — Soils that formed on the Earth's surface thousands of years ago and that are now deeply buried features of vanished landscapes have been found to be rich in carbon, adding a new dimension to our planet's carbon cycle. The finding, reported today (May 25, 2014) in the journal Nature Geoscience, is significant as it suggests that deep soils can contain long-buried stocks of organic carbon which could, through erosion, agriculture, deforestation, mining and other human activities, contribute to global climate change. "There is a lot of carbon at depths ...

Study identifies how signals trigger cancer cells to spread

Study identifies how signals trigger cancer cells to spread
2014-05-25
May 25, 2014 — (Bronx, NY) — Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered a signaling pathway in cancer cells that controls their ability to invade nearby tissues in a finely orchestrated manner. The findings offer insights into the early molecular events involved in metastasis, the deadly spread of cancer cells from primary tumor to other parts of the body. The study was published today in the online edition of Nature Cell Biology. To migrate from a primary tumor, a cancer cell must first break through surrounding connective ...

Scientists discover potential new target for cancer immunotherapy

2014-05-25
HOUSTON -- Scientists have found a way to target elusive cells that suppress immune response, depleting them with peptides that spare other important cells and shrink tumors in preclinical experiments, according to a paper published online by Nature Medicine. "We've known about these cells blocking immune response for a decade, but haven't been able to shut them down for lack of an identified target," said the paper's senior author, Larry Kwak, M.D., Ph.D., chair of Lymphoma/Myeloma and director of the Center for Cancer Immunology Research at The University of Texas MD ...

Researchers map the epic evolution of a 'ring species'

Researchers map the epic evolution of a ring species
2014-05-25
The Greenish Warbler, long considered an idealized example of a single species that diverged into two as it expanded its range, has a much more checkered family history than biologists previously realized. Ring species are a continuous loop of related populations, each adapted to its local environment, with two terminal populations in the loop meeting but now unable to mate. But an in-depth genomic analysis published today in Nature by University of British Columbia researchers reveals that the Greenish Warbler's genetic migration through central Asia involved periods ...

Advanced light

Advanced light
2014-05-25
Michael Lewis's bestselling book "Flash Boys" describes how some brokers, engaging in high frequency trading, exploit fast telecommunications to gain fraction-of-a-second advantage in the buying and selling of stocks. But you don't need to have billions of dollars riding on this-second securities transactions to appreciate the importance of fast signal processing. From internet to video streaming, we want things fast. Paul Lett and his colleagues at the Joint Quantum Institute (1) specialize in producing modulated beams of light for encoding information. They haven't ...

Sound and vision: Visual cortex processes auditory information too

2014-05-25
Scientists studying brain process involved in sight have found the visual cortex also uses information gleaned from the ears as well as the eyes when viewing the world. They suggest this auditory input enables the visual system to predict incoming information and could confer a survival advantage. Professor Lars Muckli, of the Institute of Neuroscience and Psychology at the University of Glasgow, who led the research, said: "Sounds create visual imagery, mental images, and automatic projections. "So, for example, if you are in a street and you hear the sound of an ...

Brain imaging reveals clues about chronic fatigue syndrome

2014-05-24
A brain imaging study shows that patients with chronic fatigue syndrome may have reduced responses, compared with healthy controls, in a region of the brain connected with fatigue. The findings suggest that chronic fatigue syndrome is associated with changes in the brain involving brain circuits that regulate motor activity and motivation. Compared with healthy controls, patients with chronic fatigue syndrome had less activation of the basal ganglia, as measured by fMRI (functional magnetic resonance imaging). This reduction of basal ganglia activity was also linked with ...

Slowing the insect invasion: Wood packaging sanitation yields US $11.7 billion net benefit

2014-05-24
The emerald ash borer (Agrilus plantipenis), a recent insect immigrant to North America carried in with the wooden packing material of imported goods, is projected to cause over a billion dollars in damages annually over the next decade. International standards now require expensive fumigation or heat treatment of wood pallets and crates to prevent the inadvertent import of new wood boring insect pests in shipping materials. Preventative treatment is worthwhile when the cumulative damages of widening infestations are considered, report scientists in Ecological Society ...

LAST 30 PRESS RELEASES:

Chung-Ang University researchers unveil the biogenesis and role of transfer RNA fragments in cancer progression

Secret of the female orgasm uncovered by psychologists

Breakthrough in zinc-based rechargeable batteries: A safer, sustainable alternative

"Superman" bacteria offer a sustainable boost to chemical production

FunMap reveals a functional network of genes and proteins in human cancer

First full characterization of kidney microbiome unlocks potential to prevent kidney stones

IMDEA Software researchers present MixBuy, a protocol for secure and privacy-preserving digital purchases

Having a good breakfast reduces cardiovascular risk

New study reveals provincial and territorial inequities and inadequacies in access to medications and treatment for cardiovascular conditions in Canada

Pre-seed funding to recolor the world greener

New research unlocks jaw-dropping evolution of lizards and snakes

Cardiorespiratory fitness linked to preservation of cognitive abilities in older age

Around 1 in 5 of the world’s under 50s living with genital herpes (HSV)

Cutting early life exposure to parental smoking may lower MS risk in genetically prone

High-flow nasal oxygen vs noninvasive ventilation in patients with acute respiratory failure

Flexible hibernation could help hedgehogs adapt to environmental changes

What is a unit of nature? New framework shows the challenges involved with establishing a biodiversity credit market

NYCEDC and NYU Tandon launch applications for new digital game design incubator

Soda taxes don’t just affect sales. They help change people’s minds.

Early restrictive vs liberal oxygen for trauma patients

Enabling AI to explain its predictions in plain language

A greener, cleaner way to extract cobalt from ‘junk’ materials

Better environmental performance boosts profits and cuts costs

Making self-driving cars safer, less accident prone

Rethinking the quantum chip

When does waiting stop being worth it?

Nationwide study looks at when and where EV owners use public charging stations

A new discovery about the source of the vast energy in cosmic rays

Cancer ‘fingerprint’ can improve early detection

Rethinking the brain pacemaker: How better materials can improve signals

[Press-News.org] DNA nanotechnology places enzyme catalysis within an arm's length