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Dundee scientists probe healthy protein enzyme process

Test tubes
Image caption The team at Dundee University have discovered the inner workings of O-GlcNAc transferase

Researchers at Dundee University have discovered the inner workings of an enzyme which plays a part in the development of a number of diseases.

The team has been studying O-GlcNAc transferase (OGT), which regulates O-GlcNAc. The reaction is important for healthy cells.

Inappropriate levels of the compound O-GlcNAc are known to exist in some forms of cancer, diabetes and dementia.

It is thought inhibiting OGT could slow the progression of those diseases.

Professor Daan van Aalten and his team at the University's College of Life Sciences have been studying how proteins in the cell are regulated by O-GlcNAc.

Healthy cells

The team has now uncovered the process by which the enzyme O-GlcNAc transferase (OGT) works, which is the master regulator of O-GlcNAc in the cell.

Prof van Aalten said: "The reaction of this enzyme is important for keeping proteins in the cell in a healthy state, and when this is misregulated you get diseases.

"We knew that OGT is a very, very important enzyme and without it cells are not viable, but that was previously all that was really known about the workings of it.

"Now we understand how this enzyme works we can make inhibitors against it."

Groundwork laid

O-GlcNAc is essential for human function, but also affects the development of diseases such as cancer, diabetes and dementia.

Prof Aalten added: "If you have an inhibitor you can tune down the activity of the enzyme rather than removing it altogether, and in that way probe its role in disease progression"

"This paper sets the groundwork for designing inhibitors that can be used to probe the role of O-GlcNAc in these different diseases.

"For example, we will be able to look at how bringing O-GlcNAc back to normal levels affects tumour progression.

Possible treatments

Prof Aalten hoped the research could lead to drugs which could slow the development of certain diseases.

He added: "We will be able to study the role of it in live, healthy cells and on models of these diseases to see whether there is any therapeutic effect from inhibiting this enzyme.

"We can only do this when we have an inhibitor, and we can only develop an inhibitor now that we understand the structure and mechanism of the enzyme."

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