In a sweeping new study, researchers at the University of Pennsylvania Medical Center have shown that the natural engineering principles governing electron transfer within proteins are significantly less complex than has been the prevailing view. Of the many parameters influencing the movement of electrons within biological molecules, proximity alone of the electron's origin and destination points appears to be sufficient to promote the necessary transfers: They must be no more than 14 angstroms apart.

Electron transfers of the kind investigated represent the fundamental atomic-level exchanges that underpin the energy economies of all living things. They occur between so-called reduction-oxidation centers, or redox centers, within proteins. Reduction is the receipt of an electron, and oxidation is the release of an electron. The transfers are accomplished by means of a nearly instantaneous quantum mechanical phenomenon called tunneling: The electrons tunnel through the protein from one redox center to the next. About a third of all known proteins are electron-transfer proteins.

The new findings have some important implications. They suggest, first, that many of the long-analyzed structural details of electron-transfer proteins did not evolve as necessary to their function, but are instead the happenstance result of other factors. Nature, it would appear, recognizes a point of diminishing returns in the evolutionary refinement of biological mechanisms, opting in this case for a flexible, more robust system over an optimized, finely tuned one that might be more vulnerable to disruption by mutations. Second, the results point to a greatly simplified approach to the design of entirely new biologically active molecules, likely to be of immediate use in drug development efforts, and construction of such molecules is already under way at Penn. A report on the study appears in the November 4 issue of Nature.

"What we're saying in this study is that many
'"/>

Contact: Franklin Hoke
hokef@mail.med.upenn.edu
215-349-5659
University of Pennsylvania School of Medicine
3-Nov-1999