Study shows how bioactive substance inhibits important receptor

The innate immune system is regulated by the A2A receptor. For the first time, researchers at the University of Bonn have been able to show how an important inhibitor interacts with the receptor. In the future, the results will allow the targeted search for the molecule that gives the innate immune system more punch. They could be used in the fight against cancer, but also against brain diseases such as Alzheimer's or Parkinson's. The final version of the study has been published.

Thieves like to toss a chop over the fence in order to hide sleeping pills before breaking into a mansion. The watchdogs get down to their second dinner and fall asleep. After that, the jewels of the lady of the house don't change hands very much.

Tumor cells cast out sleeping pills that paralyze the immune system in the same way. They surround themselves with a cloud of a messenger. They disabled the body's own killer cells, which would otherwise cause the cancer cells to die.

This is because the A2A receptors is located on the surface of the immune cells. The defensive troops were knocked out by this. The paralyzing effect of adenosine can be prevented by blocking the A2A receptor.

Bombardment with X-rays.

The Pharmaceutical Institute of the University of Bonn is conducting a study. It is the first time in the world that this has been achieved with preladenant-like substances.

The crystal diffracts the X-rays. The way it is done allows us to deduce the spatial structure of the complex right down to the arrangement of individual atoms.

The researchers were able to show which points of the A2A receptor preladenant bind. It is now possible to modify the inhibitor to give it better properties. Drugs should not be broken down too quickly if they have the strongest effect. Claff says that the study will make it easier to maximize the substance.

A2A is part of a group that regulates key functions in the body. They span the inside of cells. The part of them that sits on the outside is a sensor. The part protrudes into the cell when it does. This causes certain genes to be activated.

The dye is bound to the molecule.

Christa Müller, who is also a member of the Transdisciplinary Research Areas (TRA) and Life and Health, says that the receptors are important because of their central position. This is bad for X-ray structural analyses because it takes days, sometimes even weeks, tocrystallize.

They were able to attach a dye to the preladenant with a kind of string. The length and flexibility of the nano string ensures that the inhibitor is not blocked from binding to the receptor.

The methods we have developed in Bonn in recent years will allow us to decipher the structure of such and other cell membrane proteins in the future.

More information: Tobias Claff et al, Single Stabilizing Point Mutation Enables High‐Resolution Co‐Crystal Structures of the Adenosine A 2A Receptor with Preladenant Conjugates, Angewandte Chemie International Edition (2022). DOI: 10.1002/anie.202115545 Journal information: Angewandte Chemie International Edition Citation: Study shows how bioactive substance inhibits important receptor (2022, March 25) retrieved 25 March 2022 from https://phys.org/news/2022-03-bioactive-substance-inhibits-important-receptor.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.