Study maps design and system of a membrane enzyme that assumes part in inflammation, cancer

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• Source: Karolinska Institutet


• Date: 21 Mar,2021

Most drugs operate via the membranes that surround the body’s cells. The analysis, which is printed in the journal Nature Communications, can make a significant contribution to the development of potential drugs.

The cells’ equal to organs, the organelles, are enclosed by membranes. Embedded in the cell’s external and internal membranes are proteins that regulate a great number of vital functions. Nearly half of all drugs are effective via membrane proteins, such as enzymes, receptors and transporters.

Researchers at Karolinska Institutet have now, with the assistance of X-ray crystallography, molecular dynamics simulations and biochemical methods, been able to ascertain the 3D structure and mechanism of an important enzyme embedded in the cell’s nuclear membrane.

The membrane enzyme MGST2 (Microsomal Glutathione S-Transferase two ) is the engine of a biochemical process which leads to oxidative stress and the formation of oxygen radicals and, then, DNA damage and cell death.

“Membrane proteins are hard to study and it’s fantastic that we’ve managed to ascertain the crystal structure for MGST2 at high resolution,” says the study’s first author Madhuranayaki Thulasingam, researcher in the Department of Medical Biochemistry and Biophysics, Karolinska Institutet. “One of this study’s findings is that MGST2 is made up of three functional units which are controlled in a remarkably sophisticated manner. The three units are involved in mutually coordinated motions, taking turns to perform the enzyme’s function one active unit at a time.”

The results provide valuable information on the molecular regulation of different members of the receptor family, many of which are important targets for future drug development.