With this tool, Andrew J. Rader, Ph.D., assistant professor of physics, has identified a mechanism for cooperative behavior within an entire molecule, a finding that suggests that in the future it may be possible to design drugs that target anywhere along the length of a molecule's communication pathway rather than only in a single location as they do today. The discovery holds promise for increasing the likelihood of therapeutic success.
The study, "Correlating Allostery with Rigidity" is published in the current issue of Molecular BioSystems, a journal of the Royal Society of Chemistry.
Microorganisms frequently contain enzymes, protein molecules that carry out most of the important functions of cells, not present in human cells. Blocking these enzymes can stop or kill a harmful invader.
Drugs are often developed to block or restrict the function of such enzymes, thereby treating the underlying infectious disease they convey. These drugs often target specific chemical sites on bacterial or viral enzymes, and alter the enzymes so they no longer function. Unfortunately, microorganisms can evolve enzymes that are impervious to these drugs, resulting in drug resistant organisms.
"With the growth of drug resistant organisms, it is increasingly important that we gain a better understanding of what makes enzymes within cellular proteins do what they do, so that we can develop alternative approaches to targeting these proteins, shutting down enzymes and killing these superbugs," said Rader, first author of the study.
He has found that the "poking" of one spot on the rigid pathway connecting regions within proteins produces communication along the entire pathway, indicating that drugs could be targeted to multiple locations on the pathways that had not developed drug resistance and could travel to where needed. His new method identified more than twice as many communication pathways as previous studies.
To use the analogy of a railroad track, dislocating a single rail, anywhere on the track, effects the entire track as trains cannot travel from one end to the other due to the rail that is out of alignment. Returning the rail to its proper location makes the entire track function normally. In the case of the rigid pathways within proteins, affecting a single chemical locus on the pathway affects the entire pathway.
"We now see in these rigid pathways that we can effect something at a distance. This holds great potential for drug targeting. We can do something at one site on the pathway, where drug resistance is not an issue, and it will affect another, perhaps turning an enzyme off and eliminating drug resistance. It's too early to say whether we can successfully counter tuberculosis, Methicillin-resistant Staphylococcus aureus [MRSA] and others of the growing number of multidrug resistant organisms this way, but it's a promising approach well worth further exploration," said Rader.
This study by Rader, co-authored by graduate student Stephen M. Brown, was funded by the Department of Physics, School of Science at IUPUI.
Mol. BioSyst., 2011, 7, 464-471
The School of Science at IUPUI is committed to excellence in teaching, research and service in the biological, physical, behavioral and mathematical sciences. The School is dedicated to being a leading resource for interdisciplinary research and science education in support of Indiana's effort to expand and diversify its economy. For more information, visit www.science.iupui.edu
Cindy Fox Aisen | EurekAlert!
Researchers target protein that protects bacteria's DNA 'recipes'
21.08.2018 | University of Rochester
Protein interaction helps Yersinia cause disease
21.08.2018 | Schwedischer Forschungsrat - The Swedish Research Council
There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.
The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
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....
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
21.08.2018 | Ecology, The Environment and Conservation
21.08.2018 | Life Sciences
21.08.2018 | Power and Electrical Engineering