Behaviour of Enzyme Linked to Alzheimer's, Cancer Demystified in New Study

Complex computer simulations are being used by scientists to shed light on the workings of a crucial protein that, when malfunctioning, may cause Alzheimer's and cancer.

"Proteins always 'talk' to each other inside cells, and they pass information about what happens to the cell and how to respond promptly. Failure to do so may cause uncontrollable cell growth that leads to cancer or cause malfunction of a cell that leads to Alzheimer's disease," explained Margaret Cheung, of University of Houston.

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"Understanding a protein inside cells - in terms of structures and enzymatic activity - is important to shed light on preventing, managing or curing these diseases at a molecular level," said Cheung.

Cheung used computer models that simulate the environment inside a cell. Biochemists typically study proteins in water, but such test tube research is limited because it cannot gauge how a protein actually functions inside a crowded cell, where it can interact with DNA, ribosomes and other molecules.

Scientists had previously believed that a PGK enzyme shaped like Pac-Man had to undergo a dynamic hinge motion to perform its metabolic function.

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However, in the computer models mimicking the cell interior, Cheung found that the enzyme was already functioning in its closed Pac-Man state in the jam-packed surrounding.

In fact, the enzyme was 15 times more active in the tight spaces of a crowded cell.

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This shows that in cell-like conditions the function of a protein is more active and efficient than in a dilute condition, such as a test tube. This finding can drastically transform how scientists view proteins and their behaviour when the environment of a cell is taken into account.

"This work deepens researchers' understanding of how proteins function, or don't function, in real cell conditions.

"By understanding the impact of a crowded cell on the structure, dynamics of proteins can help researchers design efficient therapeutic means that will work better inside cells, with the goal to prevent diseases and improve human health," said Antonios Samiotakis, lead author of the study.

The results were published in the journal Proceedings of the National Academy of Sciences.

Source-ANI