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!
Making fuel out of thick air
08.12.2017 | DOE/Argonne National Laboratory
‘Spying’ on the hidden geometry of complex networks through machine intelligence
08.12.2017 | Technische Universität Dresden
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications
Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...
Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.
The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
11.12.2017 | Physics and Astronomy
11.12.2017 | Earth Sciences
11.12.2017 | Information Technology