Biochemical ‘action shots’ with SLAC’s X-ray laser could help scientists develop synthetic enzymes for medicine and answer fundamental questions about how enzymes change during chemical reactions.
A research team at the Department of Energy’s SLAC National Accelerator Laboratory is using the Linac Coherent Light Source (LCLS) to study an enzyme found in plants, bacteria and some animals that repairs DNA damage caused by the sun’s ultraviolet (UV) light rays.
By studying this enzyme, called DNA photolyase, with the ultrabright and ultrafast pulses of the LCLS X-ray laser, researchers finally have the opportunity to watch the enzyme in action as it catalyzes a chemical reaction in real time and at the atomic scale to resolve longstanding debates about how these enzymes work. Ultimately, this knowledge could be used to engineer improved synthetic versions of enzymes that drive crucial reactions in biological systems, or to produce novel enzymes that do not exist in nature.
“The biochemical reactions performed by enzymes are at the heart of the adaptability and efficiency of living things,” says Thomas Joseph Lane, an associate staff scientist at LCLS. “But the details of how enzymes work is hidden in chemical processes that occur on extremely short timescales, down to millionths of a billionth of a second, so we needed LCLS to reveal their secrets.”
A Powerful Repair Machine
In just a few seconds, ultraviolet light from the sun can damage DNA by creating hundreds of unwanted links within DNA’s double helix. These modifications make the genetic material bulky and unreadable by DNA replication tools, leading to permanent mutations that can cause cancer and other diseases if left unrepaired.
But the same sunlight that carries damaging UV rays also contains blue light that can induce photolyase to quickly repair any DNA damage.
Photolyase is thought to be one reason why plants – which have hours of exposure to the sun each day – are less susceptible to UV damage than humans, who lack photolyase. Humans and other mammals must fall back on alternative DNA repair mechanisms (or avoid going out into the sun altogether).
Using an Ultrafast X-ray Camera
With LCLS, researchers now have access to some of the fastest and brightest X-ray laser pulses in the world to study how living things defend themselves from UV damage.
Earlier this year, for instance, a team of scientists led by Thomas Wolf, an associate staff scientist at SLAC, used LCLS to see the first step of a protective process that prevents UV damage in the DNA building block thymine.
“Before LCLS, other X-ray ‘cameras’ were too slow,” Lane explains. “Trying to precisely image enzymes and other proteins with those X-ray sources would be like trying to take an action shot of Michael Phelps swimming with an old camera. You would only get a few blurry images over his entire 100-yard butterfly event, which would hardly make for an exciting or informative photo.”
But with LCLS, he says, “Imagine a series of high-resolution shots in sequence – you would be able to capture every drop of water and every twist of Phelps’ wrist as he butterflies. That’s what LCLS lets us do when visualizing enzyme activity.”
Building Better Enzymes
In contrast to Wolf’s experiment on how DNA protects itself from damage, Lane’s team is studying how photolyase repairs UV damage once protective mechanisms have failed. Photolyase can be controlled with great precision by exposing it to light, making it an ideal enzyme to study using laser-generated light.
To see photolyase chemistry in detail, the researchers activated the enzyme with a carefully controlled light pulse from a laser. They subsequently exposed the enzyme to the LCLS-generated X-ray pulse, creating a characteristic X-ray scatter pattern in a specialized detector. The analysis of scattered X-ray data revealed chemical and structural changes in the enzyme at atomic level and occuring at a time scale of a millionth of a billionth of a second.
Top: An optical microscope image of crystallized photolyase enzymes before they are probed by the LCLS X-ray laser. Bottom: An X-ray diffraction pattern from the photolyase crystals. These patterns, made by X-rays interacting with atoms in the crystal, are used to determine the structure of the molecule. (Thomas Joseph Lane/SLAC National Accelerator Laboratory)
One of the ultimate goals of studying the enzymatic DNA repair process is to engineer synthetic enzymes that mimic but are even better than those found in nature.
“There are still some major gaps in our understanding of how enzymes work, highlighted by the fact that man-made enzymes have yet to match nature’s performance,” says Lane. “We hope our experiments here at LCLS will help us bridge those gaps, getting us closer to understanding and harnessing the chemistry living things do every day.”
The Latest on: Enzymes
- Global Industrial Enzymes Market Size & Share Witnessing Consistent Growth—Projected to Reach worth USD 9.2 Billion by 2027 | BlueWeaveon October 12, 2021 at 8:00 am
The industrial enzymes market is witnessing growth due to rising environmental concerns, increased demand for bioethanol, and developments in R&D efforts. Furthermore, the multifunctional advantages ...
- Revealing the Efficient Enzymes of Methane-Producing Microbeson October 12, 2021 at 4:15 am
The atmospheric levels of methane, which is known to be a potent greenhouse gas, have been steadily increasing for many years. Methanogenic archaea are | Microbiology ...
- Pumpkin Enzymes Have Become a Popular Skin Care Ingredient—How Do They Work?on October 11, 2021 at 6:20 am
While lattes and pie are, of course, at the forefront of those conversations, we want to focus in on one of the squash's beauty-centric iterations: pumpkin enzymes. Believe it or not, this ingredient ...
- Digestive Enzymes Market 2021: Major Manufacturers, Market Dynamics, Industry Trends, Share, Size and Forecast to 2026on October 11, 2021 at 1:33 am
Global “Digestive Enzymes Market” research report provides deep insight into the current and future state of the ...
- Ligases Enzymes Market 2021: Top Manufacturers, Growth Factor, Market Size, Share, Marketing Strategy and Forecast to 2026on October 11, 2021 at 1:25 am
Global “Ligases Enzymes Market” research report provides deep insight into the current and future state of the ...
- Industrial Enzymes Market demand, Growth, Trends 2021on October 8, 2021 at 2:41 am
Global industrial enzymes market was worth USD 6.0 billion in 2020 and is further projected to reach USD 9.2 billion by 202 ...
- Enzymes in Biofuel Market (2021-2027) Growth Forecast At CAGR By Noor Creations, Enzyme Solutions, Novozymes, Royal DSMon October 8, 2021 at 12:54 am
The new study on the Global Enzymes in Biofuel Market 2021-2027 analyzes the crucial capabilities, key infrastructures, major organizations, evaluates measures to attain potential success in the ...
- Industrial Enzymes Market Size to Reach USD 8400.4 Million by 2027 at a CAGR of 4.9% | Valuates Reportson October 7, 2021 at 9:58 am
BANGALORE, India, Oct. 7, 2021 /PRNewswire/ -- The Industrial Enzymes Market is Segmented by Type (Saccharifying Enzyme, Amylase, Protease, Lipases), by Application (Food and Beverage ...
- Animal Feed Enzymes Market Outlook, Demand, Regional Analysis, CAGR Value and Growth Forecast for the Period 2017 to 2026on October 6, 2021 at 12:30 am
The global animal feed enzymes market has a highly consolidated vendor landscape, says Transparency Market Research, in a recently published report. Azelis Holdings, Novus International, Bio-Cat, ...
via Google News and Bing News