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Scientists reveal fine detail of cell's energy machinery

The structure of the pump, a key enzyme in bacterial respiration, reveals for the first time one of the molecular mechanisms that underpins cellular respiration, and confirms a Nobel Prize-winning theory proposed over 40 years ago by Briton Peter Mitchell.

Professor So Iwata and colleagues from the Laboratory of Membrane Protein Crystallography, Imperial College Centre for Structural Biology describe in Science today what the enzyme formate dehydrogenase-N looks like to a resolution of 1.6 angstroms - or one hundred millionth of a centimetre *1.

"From bacteria to humans, the mechanism of energy conversion is shared by a wide range of organisms, and solving this enzyme's structure provides a valuable insight into the molecular machinery of life," said Professor Iwata.

Formate dehydrogenase-N, a bacterial enzyme involved in nitrate respiration, lies in the membranes of cells. Iwata's Laboratory of Membrane Protein Crystallography is one of a small number around the world that focuses on solving membrane protein structures using X-ray crystallography.

Membrane proteins are technically difficult targets for structural biologists to solve. Fewer than 30 membrane protein structures are presently known, compared with over 10,000 soluble protein structures, estimates Professor Iwata.

"Many genetic disorders such as cystic fibrosis are directly related to membrane proteins, and as many as 70 per cent of drugs currently available act through membrane proteins.

"Solving the structure of membrane proteins is essential to facilitate the rational design of effective drugs and to develop new therapies for genetic diseases," he said.

Their work with the bacteria E. coli provides the first real evidence for the 'chemiosmotic' theory proposed by Dr Peter Mitchell in 1961. Initially dismissed by mainstream science, Mitchell's theory on energy conversion is now accepted as a fundamental principle in the field of 'bioenerg
'"/>

Contact: Judith H. Moore
j.h.moore@ic.ac.uk
44-0-20-7594-6702
Imperial College London
7-Mar-2002


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