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Scientists convert modern enzyme into its hypothesized ancestor

UPTON, NY - By making a single substitution in the amino acid sequence of a modern enzyme, scientists have changed its function into that of a theoretical distant ancestor, providing the first experimental evidence for the common origin of the two distinct enzyme types. The research, conducted by a team that includes scientists from the U.S. Department of Energy's Brookhaven National Laboratory and the Karolinska Institute in Stockholm, Sweden, will be published online the week of October 30, 2006, by the Proceedings of the National Academy of Sciences.

"It's as if we turned back the clock nearly 2.5 billion years, to the time when oxygen first appeared in Earth's atmosphere, to get a snapshot of how enzymes evolved to deal with reactive oxygen species," said Brookhaven biochemist John Shanklin, lead author on the paper.

Oxygen, while essential for many life processes, can also exist in potentially toxic forms, such as superoxide and hydroxyl radicals, as well as hydrogen peroxide. After the first photosynthetic organisms appeared on Earth some 2.5 billion years ago, pumping oxygen into the atmosphere, organisms with enzymes capable of deactivating these reactive oxygen species had an increased chance of survival.

Scientists have theorized that the first oxygen-detoxifying enzymes were simple oxidases, which combine reactive forms of oxygen, such as peroxide, with hydrogen ions (protons) and electrons to yield water (H2O). While these enzymes have little in common with more modern biosynthetic enzymes that mediate oxygen chemistry, they share certain structural and sequence characteristics around their active sites -- namely, a pair of iron atoms for binding oxygen within a similar four-helix bundle. These similarities suggested the possibility of a common origin, but experimental evidence was lacking -- until now.

The Brookhaven/Karolinska team had previously performed a structural comparison of the active site of a modern des
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Contact: Karen McNulty Walsh
kmcnulty@bnl.gov
631-344-8350
DOE/Brookhaven National Laboratory
30-Oct-2006


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