Chemical biology news from across RSC Publishing.
01 May 2007
Scientists are one step closer to understanding a progressive neurodegenerative disease thanks to a study into the role of an essential human protein, frataxin.
- Timothy Stemmler
Frataxin has been implicated in iron transport in the body. In Friedreich's ataxia (FRDA), an inherited disorder that causes increasing deterioration of the nervous system and affects about 1 in 50 000 people, the body is unable to make frataxin. The resulting protein deficiency affects the cells' ability to control and use iron, with debilitating consequences. According to Timothy Stemmler a structural biologist at Wayne State University, Detroit, US: 'If scientists can understand what frataxin does and how to help FRDA patients make it, we can go a long way to developing new drugs to treat or even cure these patients.'
Working towards this goal, Stemmler and his colleagues in the US and Mexico, investigated frataxin's role in the production of heme - an iron-containing protein cofactor that controls cellular processes ranging from energy production to oxygen transport. Using a combination of x-ray absorption and nuclear magnetic resonance spectroscopies, the team showed that frataxin operates as a molecular chaperone to iron, delivering the metal to ferrochelatase, the enzyme involved in assembling heme.
Docking simulation of frataxin (Ftx) (green) with the ferrochelatase (Frch) dimer.
Andrew Dancis, an expert in iron transport at the University of Pennsylvania, US, explained that the iron delivery step in the ferrochelatase synthesis of heme has been completely mysterious until now. 'Frataxin is in the right place to play a role in this process,' he said. 'Stemmler sheds light on this process by defining the human ferrochelatase binding surface with iron and frataxin, and by proposing a pathway for the iron delivery.'
Stemmler suggested that, 'if we can understand all the steps involved in the different cellular iron regulation pathways at the protein level, we can provide a universal understanding of how cells control the chemistry performed by this highly reactive element. This insight should help not only in treating FRDA,' he continued, 'but the growing number of metal regulation related human disorders as well.'
Read more about heme in the July special issue of Natural Product Reports: 'The chemistry and biochemistry of heme proteins.'
Link to journal article
Human frataxin: iron and ferrochelatase binding surface
Krisztina Z. Bencze, Taejin Yoon, César Millán-Pacheco, Patrick B. Bradley, Nina Pastor, J. A. Cowan and Timothy L. Stemmler, Chem. Commun., 2007, 1798
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