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Structure of cog at the hub of metabolism reveals anti-ageing function

The structure of a key energy-releasing enzyme found in all animals is designed to minimise free radical production, an international team of researchers report in the journal Science today.

In a startling feat of structural biology, the team visualised the entire molecular structure of succinate dehydrogenase in the bacterium E. coli, allowing them to see for the first time how the protein's three-dimensional shape helps prevent the formation of large quantities of these destructive oxygen atoms.

Formed as a by-product during cellular respiration, free radical can cause havoc in cells by reacting with DNA or the cell membrane, knocking out or impairing their function, a process linked to cellular ageing.

Professor Paul Fremont, Director of Imperial's Centre for Structural Biology, said: "Professor Iwata's group have performed an extraordinary feat in obtaining the first three-dimensional insights of succinate dehydrogenase.

"This fundamentally important and highly complex metabolic enzyme protects the bacterium from self inflicted damage and lies at the heart of the cell's energy powerhouse. It acts like a built in anti-pollution system, and has significant implications for understanding human ageing."

Professor So Iwata of Imperial College London, senior author of the paper added: "Solving the structure of succinate dehydrogenase opens up new leads in the quest to understand longevity and ageing.

"It now appears that a wide variety of genetic disorders including muscle and neurodegenerative diseases, and tumour formation, are caused by defective forms of this enzyme - as a result of increased free radical formation."

"The challenge now is to try and engineer succinate dehydrogenase to maximise its efficiency. The E. coli bacterium provides a flexible model to advance this research because the enzyme is very similar to the human version."

Cellular respiration is the process of oxidizing food m
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Contact: Judith H. Moore
j.h.moore@imperial.ac.uk
44-207-594-6702
Imperial College London
30-Jan-2003


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