Distance between atoms is key to iron protein function

December 29, 1999

ANN ARBOR---Geometry is destiny in the molecular world where small structural changes can mean big functional differences. According to University of Michigan chemist James Penner-Hahn, this is especially true for non-heme diiron proteins that use iron and oxygen to regulate important biological functions.

In a paper published in the Jan. 7 issue of Science, Penner-Hahn and colleagues describe how they used analytical techniques to probe the molecular structure of peroxide intermediates in diiron proteins. While scientists have known for years that diiron proteins carry out a variety of biological functions, recent work has shown that many of these proteins pass through a peroxide-bridged intermediate state as part of their reaction with oxygen.

Sometimes the peroxide-bridged intermediate works as part of an enzyme to activate oxygen for critical reactions, such as synthesizing DNA building blocks or converting methane into methanol. Sometimes, in a process called biomineralization, the same intermediate is used to store iron atoms within the protective protein envelope of the iron-storage protein, ferritin.

"The puzzle has been how the same intermediate can act as a catalyst with oxygen-activating enzymes, but act as a substrate with ferritin proteins," said Penner-Hahn, a U-M professor of chemistry.

The answer appears to be an unusually short distance of 2.53 angstroms between iron atoms in the peroxide-bridged ferritin intermediate---a distance about 0.5 to 1.5 angstroms shorter than that between iron atoms in other peroxide-bridged intermediates.

"Half an angstrom is miniscule compared to the size of a protein, but it's the equivalent of the Grand Canyon on an atomic scale," Penner-Hahn explained. "The shorter distance between iron atoms forces the ferritin diiron site into an unusual geometry that should strengthen the O-O bond [the bond between oxygen atoms] and thus favor the biomineralization process, rather than oxygen activation."

The key to the study's success was collaboration with experts from different disciplines, said Penner-Hahn. "No one set of measurements could have provided all the information needed to complete the study," he added.

Molecular structures of peroxide intermediates were identified by Penner-Hahn and former U-M post-doctoral fellow Jungwon Hwang. The biochemistry and molecular biology of ferritin have been documented by Elizabeth C. Theil, a senior research scientist at CHORI (Children's Hospital Oakland Research Institute) in Oakland, Calif. Trapping of the peroxide intermediate and its characterization by Mossbauer spectroscopy was the work of Carsten Krebs, post-doctoral fellow; Boi Hanh (Vincent) Huynh, professor of physics; and Dale E. Edmondson, professor of biochemistry, at Emory University in Atlanta. X-ray absorption data were measured at the Stanford Synchotron Radiation Laboratory, which is operated by the U.S. Department of Energy, Office of Basic Energy Sciences.

Additional research support was provided by the National Institutes of Health, National Center for Research Resources and the DOE Office of Biological and Environmental Research.
-end-
The University of Michigan
News Service
412 Maynard
Ann Arbor, MI 48109-1399

Contacts: Sally Pobojewski
pobo@umich.edu
734-647-1844


James Penner-Hahn
jeph@umich.edu
734-764-7324


Web: http://www.umich.edu/~newsinfo

University of Michigan

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