Just as a breeze causes leaves, branches and ultimately the tree to move, enzymes moving at the molecular level perform hundreds of chemical processes that have a ripple effect necessary for life.
Previously, protein complexes were viewed as static entities with biological function understood in terms of direct interactions, but that isn’t the case. This finding, published today in PLoS Biology, may have enormous implications.
“Our discovery is allowing us to perhaps find the knobs that we can use to improve the catalytic rate of enzymes and perform a host of functions more efficiently,” said Agarwal, a member of the Department of Energy laboratory’s Computer Science and Mathematics Division.
Making this discovery possible was ORNL’s supercomputer, Jaguar, which allowed Agarwal and co-author Arvind Ramanathan to investigate a large number of enzymes at the atomistic scale.
The researchers found that enzymes have similar features that are entirely preserved from the smallest living organism – bacteria -- to complex life forms, including humans.
“If something is important for function, then it will be present in the protein performing the same function across different species,” Agarwal said. “For example, regardless of which company makes a car, they all have wheels and brakes.”
Similarly, scientists have known for decades that certain structural features of the enzyme are also preserved because of their important function. Agarwal and Ramanathan believe the same is true for enzyme flexibility.
“The importance of the structure of enzymes has been known for more than 100 years, but only recently have we started to understand that the internal motions may be the missing piece of the puzzle to understand how enzymes work,” Agarwal said. “If we think of the tree as the model, the protein move at the molecular level with the side-chain and residues being the leaves and the protein backbone being the entire stem.”
This research builds on previous work in which Agarwal identified a network of protein vibrations in the enzyme Cyclphilin A, which is involved in many biological reactions, including AIDS-causing HIV-1.
While Agarwal sees this research perhaps leading to medicines able to target hard to cure diseases such as AIDS, he is also excited about its energy applications, specifically in the area of cellulosic ethanol. Highly efficient enzymes could bring down the cost of biofuels, making them a more attractive option.
Funding for this research was provided by ORNL’s Laboratory Directed Research and Development program. Ramanathan was a graduate student at Carnegie Mellon University when this work began and now also works at ORNL. The paper is titled “Evolutionarily conserved linkage between enzyme fold, flexibility and catalysis.”UT-Battelle manages ORNL for DOE’s Office of Science.
with red and blue regions representing maximum and minimum mobility, respectively. Hydrogen bond interactions from the surface of the enzyme connect all the way to the active site and are indicated as yellow dashes. The interactions and the internal motions in Cyclophilin A are conserved from bacteria to humans.
NOTE TO EDITORS: You may read other press releases from Oak Ridge National Laboratory or learn more about the lab at http://www.ornl.gov/news. Additional information about ORNL is available at the sites below:
Twitter - http://twitter.com/oakridgelabnews
RSS Feeds - http://www.ornl.gov/ornlhome/rss_feeds.shtml
Flickr - http://www.flickr.com/photos/oakridgelab
YouTube - http://www.youtube.com/user/OakRidgeNationalLab
LinkedIn - http://www.linkedin.com/companies/oak-ridge-national-laboratory
Facebook - http://www.facebook.com/Oak.Ridge.National.Laboratory
| Newswise Science News
Staying in Shape
16.08.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik
Chips, light and coding moves the front line in beating bacteria
16.08.2018 | Okinawa Institute of Science and Technology (OIST) Graduate University
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur
What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...
08.08.2018 | Event News
27.07.2018 | Event News
25.07.2018 | Event News
16.08.2018 | Life Sciences
16.08.2018 | Earth Sciences
16.08.2018 | Life Sciences