with Judith H Moore
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.
Image
of energy-releasing enzyme |
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 destructive oxygen atoms.
Using the latest X-ray crystallography techniques, Imperial PhD
student, Rob Horsfield solved the structure of succinate
dehydrogenase. Researchers from the UK, Sweden, the United States
and Japan were then able to probe the three-dimensional structure
of the protein, to examine how the enzyme releases energy by
breaking down a derivative of glucose, succinate, to asmaller
molecule fumarate.
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 So Iwata of Imperial College London, senior author of
the paper explained: "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."
Professor Paul Fremont, Director of Imperial's Centre for
Structural Biology, added: "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."
