Breakthrough in understanding role of enzyme in disease

Oct 30, 2012

Researchers at the University of Dundee have uncovered the mechanism of an important human enzyme that plays a role in the development of debilitating diseases including cancer, dementia and diabetes.

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 an unusual chemical modification called O-GlcNAc.

The team have now explained the inner workings of the enzyme O-GlcNAc transferase (OGT), which is the master regulator of O-GlcNAc in the cell. Inappropriate levels of O-GlcNAc are known to exist in some forms of , diabetes and .

"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," explained Professor van Aalten. "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.

"This is essential for human function, but also plays a role in diseases such as cancer, and dementia. 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 "

"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.

"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 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."

The research, which was funded by the Wellcome Trust, is published today in the latest edition of the Nature Chemical Biology journal.

Explore further: 'Global positioning' for molecules

Related Stories

Hopkins team discovers sweet way to detect prediabetes

Jul 08, 2010

Having discovered a dramatic increase of an easy-to-detect enzyme in the red blood cells of people with diabetes and prediabetes, Johns Hopkins scientists say the discovery could lead to a simple, routine test for detecting ...

Chemists determine one way tumors meet their growing need

Aug 23, 2012

Behaving something like ravenous monsters, tumors need plentiful supplies of cellular building blocks such as amino acids and nucleotides in order to keep growing at a rapid pace and survive under harsh conditions. ...

Sugarcoating fruit fly development

May 29, 2009

Proteins are the executive agents that carry out all processes in a cell. Their activity is controlled and modified with the help of small chemical tags that can be dynamically added to and removed from the protein. 25 years ...

Blocking 'oh-glick-nack' may improve long-term memory

Mar 27, 2012

Just as the familiar sugar in food can be bad for the teeth and waistline, another sugar has been implicated as a health menace and blocking its action may have benefits that include improving long-term memory ...

Recommended for you

'Global positioning' for molecules

8 hours ago

In everyday life, the global positioning system (GPS) can be employed to reliably determine the momentary location of one en route to the desired destination. Scientists from the Institute of Physical and ...

Cells build 'cupboards' to store metals

Dec 17, 2014

Lawrence Livermore researchers in conjunction with collaborators at University of California (link is external), Los Angeles have found that some cells build intracellular compartments that allow the cell ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.