(Press-News.org) Researchers from IOCB Prague are furthering the understanding of how medicines work and what it takes to develop their most effective variants. In one current study, they have focused on the disease caused by the protozoan parasite Trichomonas vaginalis, especially because of the recent appearance of strains that are resistant to conventional treatment. In an effort to find a new weak spot of this parasite, the research group led by Dr. Evžen Bouřa has succeeded in preparing a key enzyme complex – the proteasome. This has made it possible to gain knowledge that is indispensable for the development of new effective medicines. The research was carried out in collaboration with colleagues from the University of California San Diego. An article presenting the work has been published in the scientific journal Nature Communications.
The proteasome is a complex protease that works as a device for recycling old proteins in cells. It is a cylindrical enzyme complex composed of seven subunits arranged in four superposed circles. When old proteins enter this cylinder, they get broken down into small pieces later used by the cell to make new proteins. If it functions incorrectly, old proteins accumulate, leading to the cell’s demise. This is why the blocking of proteasome activity is used, for example, against certain types of malignant tumours.
In the same way, it should also be possible to treat the widespread sexually transmitted infection trichomoniasis, which increases the risk of contracting HIV. The aim is therefore to identify substances that block the function of the proteasome inside Trichomonas vaginalis cells. However, the proteasome of this single-cell organism had never been satisfactorily isolated, so the research group from IOCB Prague prepared an artificial proteasome that is identical to the natural one. Curiously, they used insect cells to do so. This part of their research, on which the success of the whole project was hinged, proved the most complicated. That the team has prevailed in describing the previously unknown structure of the parasite’s proteasome is therefore of critical importance.
‘The proteasome looks the same in every animal or protozoan, but the details of this cylindrical structure differ. It is these details that we need to know in order to create a substance that is toxic to the parasite but not harmful to the human body. That is a crucial precondition for drug development. Our greatest success is that we have been able to prepare a recombinant, artificial proteasome that can provide us with the necessary information,’ explains Evžen Bouřa.
The researchers used advanced electron microscopy, allowing them to see almost every single atom. Armed with this capability, they tested the effects of two potential proteasome-inhibiting substances. They saw how they bind to the active site of the proteasome and under what circumstances the proteasome stops working, which is fatal to the cell of the parasite.
Video: Dr. Evžen Bouřa: https://youtu.be/aRS8orXfvec
Original article: Silhan, J.; Fajtova, P.; Bartosova, J.; Hurysz, B. M.; Almaliti, J.; Miyamoto, Y.; Eckmann, L.; Gerwick, W. H.; O’Donoghue, A. J.; Boura, E. Structural elucidation of recombinant Trichomonas vaginalis 20S proteasome bound to covalent inhibitors. Nat. Commun. 2024, 15, 8621. https://doi.org/10.1038/s41467-024-53022-w
IOCB Prague / Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (www.uochb.cz) is a leading internationally recognized scientific institution whose primary mission is the pursuit of basic research in chemical biology and medicinal chemistry, organic and materials chemistry, chemistry of natural substances, biochemistry and molecular biology, physical chemistry, theoretical chemistry, and analytical chemistry. An integral part of the IOCB Prague’s mission is the implementation of the results of basic research in practice. Emphasis on interdisciplinary research gives rise to a wide range of applications in medicine, pharmacy, and other fields.
END
Scientists from IOCB Prague help to improve medical drugs
2024-10-08
[Attachments] See images for this press release:
ELSE PRESS RELEASES FROM THIS DATE:
Recreating a hallmark of Parkinson's disease in human neurons
2024-10-08
Lewy bodies are a hallmark of Parkinson's disease (PD) and other related neurological conditions. Understanding why and how they develop is critical to developing better treatments. A study from The Neuro (Montreal Neurological Institute-Hospital) of McGill University, in collaboration with its Early Drug Discovery Unit, has recreated the growth of Lewy bodies in human neurons and followed their formation to gain important insight into why and how they form. Critically, they find that immune challenge is important for this process, identifying a previously unknown link between the immune system and neurological disease.
Lewy ...
Solar-powered desalination system requires no extra batteries
2024-10-08
MIT engineers have built a new desalination system that runs with the rhythms of the sun.
The solar-powered system removes salt from water at a pace that closely follows changes in solar energy. As sunlight increases through the day, the system ramps up its desalting process and automatically adjusts to any sudden variation in sunlight, for example by dialing down in response to a passing cloud or revving up as the skies clear.
Because the system can quickly react to subtle changes in sunlight, it maximizes the utility of solar energy, producing large quantities of clean water despite ...
When it comes to emergency care, ChatGPT overprescribes
2024-10-08
Generative AI still needs to find the right balance between too little and too much care before it can help doctors make decisions in the Emergency Department.
If ChatGPT were cut loose in the Emergency Department, it might suggest unneeded x-rays and antibiotics for some patients and admit others who didn’t require hospital treatment, a new study from UC San Francisco has found.
The researchers said that, while the model could be prompted in ways that make its responses more accurate, it’s still no match for the clinical judgment of a human doctor.
“This ...
Speakers to tackle global health challenges at WISH 2024
2024-10-08
7 October 2024. Doha, Qatar – The World Innovation Summit for Health (WISH) has today released the first details of speakers confirmed for its upcoming global conference, to be held on 13 and 14 November 2024.
Among those featured at the summit will be WISH executive chair Lord Ara Darzi of Denham and Médecins Sans Frontières’ international president Christos Christou.
Lord Darzi, who recently led an independent investigation on the state of the National Health Service in England, will ...
Mental health app could help prevent depression in young people at high risk
2024-10-08
A cognitive behavioural therapy (CBT) app has been found to significantly prevent increases in depression in young people who are at high risk - and could be implemented as a cost effective public mental health measure.
Globally, concern is growing about the high and steadily increasing rates of anxiety and depression in young people. Effective and scalable ways of preventing poor mental health in this group are needed, and digital tools such as mobile apps have been proposed as part of the solution.
Whilst there is emerging evidence ...
Dogs contaminate London ponds with parasite medications
2024-10-08
Most dog owners didn’t know that flea and tick treatments are dangerous to aquatic life, suggesting more awareness could ease the problem.
A study on Hampstead Heath shows that ponds where dogs are allowed to swim contain levels of two pesticides harmful to invertebrate life.
These pesticides, imidacloprid and fipronil, are used as parasite treatments for flea and tick infestations in cats and dogs, using ‘spot-on’ formulas and flea collars. This is despite these chemicals being banned for agricultural use in 2018 due to their toxicity to bees and other ...
Oh my meniscus: age poses risk of further knee injury in children
2024-10-08
Growing pains are common in maturing children, but sometimes this growth can be irregular and cause injury. Discoid lateral meniscus (DLM), a misshapen knee cartilage, is one such occurrence that can degenerate into osteochondritis dissecans, a joint disorder where the bone and joint begin to separate from the rest of the bones. It has been reported that osteochondritis dissecans of the femoral condyle occurs in approximately 14.5% of cases of DLM, but there has been little analysis of its treatment to date.
Dr. Ken Iida and Specially ...
Increase access to nature in all daily environments and in education
2024-10-08
Although access to nature is a basic human right, people’s actual use of green spaces is subject to inequalities. A Kobe University-led research team analyzed what conditions make it more likely that people are exposed to nature across generations: the availability of green spaces around where they live, work and shop, as well as nature relatedness and past natural experiences. Their findings may inform policies for urban planning and education for the improvement of human health.
Visiting green spaces is good for people’s health, both psychologically and physiologically. ...
AI speeds up the discovery of energy and quantum materials.
2024-10-08
Researchers from Tohoku University and the Massachusetts Institute of Technology (MIT) have unveiled a new AI tool for high-quality optical spectra with the same accuracy as quantum simulations, but working a million times faster, potentially accelerating the development of photovoltaic and quantum materials.
Understanding the optical properties of materials is essential for developing optoelectronic devices, such as LEDs, solar cells, photodetectors, and photonic integrated circuits. These devices are pivotal in the semiconductor industry's current resurgence.
Traditional means of calculation using the basic laws of physics involve complex ...
An efficient way to hydrogenate nitrogen-containing aromatic compounds has been developed
2024-10-08
Successful reduction of the chemical manufacturing industry’s environmental impact relies on finding a greener way to make the chemical building blocks for common and massively consumed compounds.
It’s no secret manufacturing processes have some of the most impactful and intense effects on the environment, with the chemical manufacturing industry topping the charts for both energy consumption and emissions output. While this makes sense thanks to the grand scale in which manufactured chemicals are involved in daily life, it still leaves a lot to be desired for sustainability’s sake. By focusing on renewable energy sources and alternative methods for creating the ...