‘Pac-Man with a ponytail’ proteins regulate everything from night vision to heartbeats – studying what GRKs look like could improve an array of drugs
Each cell in your body depends on accurate communication with other cells to work properly. In the midst of this process, there are molecular keys that convert communication signals in the body and stop them. These molecules are major health and disease players. One of these molecular keys Kinaz Protein GOr GRKS for a short period.
From vision to heart function and cell growth, GRKS plays a vital role in maintaining physiological balance. When they go Cardiovascular diseasesand Inflammatory diseases Such as rheumatoid arthritis and multiple sclerosis, Neurological degenerative diseases Like Alzheimer’s, and Multiple types of cancer.
Their participation in a wide range of diseases makes GRKS an attractive target of drugs. around 30 % to 40 % of all medications Currently on the market focus on these proteins. However, the design of drugs that target GRKS selectively is a difficult task. Because they are Stylistical similarity For each other and for other proteins, the particles associated with one GRK may also be associated with many other enzymes and cause unwanted side effects.
A better understanding of how GRKS interacts with their goals can help researchers develop better drugs. So practical in Tesmer lab Bordeaux University focuses on detecting more information about GRKS.
How does Grks look?
What GRKS seekers know has advanced greatly over the past two decades, revealing the complex mechanisms in which they work.
The ability to physically look at the proteins is very useful for developing the drug. Seeing a protein structure is similar to looking at a panoramic puzzle – you can find the lost piece by knowing its shape. Likewise, knowing the form of protein helps scientists design the molecules that perfectly fit with them, making medicines more effective.
GRKS consists of several units, or fields, serving a specific purpose. Together, these units are combined in a Backman -like structure with a ponytail.
Kinaz field – Back Man It is the motivation center where the protein performs its main work: Add a phosphate set To its goal to control its activity. It contains two sub -clubs – a small and one large clove – connected to a detailed that can open and close. Like PAC-Man, this field is closed around reactive materials and reopens the products.
RH – Ponytail – Kinaz domain settles. It guides and runs GRK to the target protein.
Humans have seven GRKS, each specialist in different tissues and functions, and each unique in the structure. Some organize vision, while others affect your mind, kidneys and immunity, among other things. Her structural differences dictate how they interact with their goals, and understanding these differences is the key to the design of medicines that can be selectively targeted.
In 2003, researchers discovered the laboratory where I work as the first well -known structure for GRK – Specifically, GRK2Which is involved in the functions of the heart and the spread of cells – using a technique called Photography of molecular crystals. This included the bombing of the GRK2 sample with X -rays and tracking, which is bounced to determine where each atom of protein is.
The current situation of GRK research
By determining how to arrange the three GRK2 units and wherever their target molecules are connected, I, his colleagues and colleagues can design drugs that interact strongly with GRK2.
For example, in 2012, one of my colleagues discovered that the antidepressant It can prevent Paxil GRK2. To build on this discovery, our team designed similar forms to Paxil to determine those that effectively prevent GRK2 and choose. The goal was to develop treatments that could target GRK2 diseases such as heart failure and breast cancer without interfering with other proteins, thus reducing side effects.
After selecting the Paxil shape when connecting GRK2, we designed a series of derivative compounds that fit better with the active GRK2 site – pieces of missing panorama. Some of these vehicles managed to better prevent GRK2 compared to Paxil, and improve The ability of the heart muscle cells to contract. While the research is still in its early stages, the results we have found indicate that these compounds can be used to treat heart failure.
An important part of the story is what GRK2 looks like when it is associated with its primary goal in the cells. These protein complexes change dramatically, making traditional photography methods very difficult.
However, recent developments in photography made it possible to determine the structure of these molecules. Cool electronic microscope, or Cryo-EemFlash freezes proteins and hides them with electrons to capture their structure. These studies have revealed so far what Grk1 and Grk2 It looks when they are associated with different targeted proteins, providing critical visions on how they work.
My work focuses on revealing how the GRK2 function differs from GRK1. These proteins play different physiological roles – GRK1 mainly organizes vision, while GRK2 is involved in heart function and cell spread. Determining structural differences in various GRKS researchers will help the design of drugs that target only GRK, thus preventing side effects.
By combining advanced photography techniques with research contracts, scientists in laboratory and others hope to open the full therapeutic capabilities of GRKS, providing specific treatments for a wide range of diseases.
This article has been republished from ConversationAn independent, non -profit news organization brings you facts and trusted analysis to help you understand our complex world. Written by: Priyanka Nikeand Bordeaux University
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Priyanka Naik receives funding from Bordeaux University. The Tesmer laboratory, which was discussed here, is funded by the Bordeaux Institute for Cancer Research, National Health Institutes and Waltur Cancer.
