NEWS OF THE WEEK BIOINORGANIC
CHEMISTRY
PUTTING THE OH WHERE IT BELONGS Study shows how P450s hydroxylate hydrocarbons but not themselves
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NLY A HANDFUL OF HEME
proteins—for example, the medically important family ofcytochrome P450 enzymes that metabolize drugs in the b o d y are capable of attaching hydroxyl groups to inert hydrocarbon substrates. A new X-ray absorption study of a model member of this protein class hints at what allows these enzymes to create reactive iron intermediates that can perform this demanding chemistry without destroying themselves. The active sites of cytochrome P450s contain a heme cofactor whose iron center is coordinated to the protein via a cysteine thiolate. During catalysis, these enzymes are thought to use dioxygen to generate an Fe(IV) = 0 radical species. This highly reactive ferryl radical species is thought to abstract hydrogen from the hydrocarbon substrate,
I R O N W I L L The cysteine that binds the heme iron in P450s allows these enzymes to oxidize inert substrates.
forming a protonated ferryl that then hydroxylates the substrate. Somehow, this highly reactive ferryl radical species performs hydroxylations without oxidizing the surrounding enzyme. "That's a remarkable feat," says MichaelT. Green, an assistant professor of chemistry at Pennsylvania State University He collaborated with chemists Harry B. Gray of California Institute of Green Technology andjohn H. Dawson of the University of South Carolina to try to figure out what allows a P450 to hydroxylate hydrocarbons without destroying itself. Since it has proven impossible to trap and study these ferryl radical
NANOTECHNOLOGY
Nantero To Move Nanotubes Into Computer Chips
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antero, a nanotechnology start-up firm, Is working with the semiconductor manufacturer LSI Logic to incorporate carbon nanotubes into high-end computer chips. If these chips go commercial next year as expected, they will represent one of the first uses of carbon nanotubes outside of the product reinforcement realm. Nantero was cofounded in 2001 by chemists Thomas Rueckes and Brent M. Segal and businessman Greg Schmergel to commercialize nanotechnology discovered by Rueckes while he was a research fellow at Harvard University. The firm has since raised more than $15 million in venture-capital financing. The company seeks to replace several existing forms of computer memory with one universal chip in which single-wall nanotubes are 14
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2004
strung over an electrode. Applying an electric field to one of the nanotubes causes it to dip down and hit an electrode, completing a circuit and creating the zeros and ones with which digital memory is formed. LSI intends to use the technology in memory chips that it will make at its Gresham, Ore., facility. Because such chips maintain data when power is turned off, they could enable "instanton" computers, Nantero says. They could also replace conventional memory in devices such as cell phones and digital cameras. Schmergel says Nantero will obtain its nanotubes from one of the "couple dozen" companies that already manufacture the materials, which are now used mostly for the purpose of reinforcing plastic products such as tennis rackets and automotive parts.-MICHAEL MCCOY
species in P450 enzymes, Green's team turned to chloroperoxidase—a closely related fungal enzyme with an identical active site— as a model system. Using X-ray absorption spectroscopy to estimate bond lengths, they show that chloroperoxidase uses a catalytic intermediate just like the protonated high-valent F e = 0 species thought to participate in P450 catalysis [Science, 3 0 4 , 1653 (2004)}. This unexpected observation "gives us an indication of how P450 enzymes manage to hydroxylate their substrates," Green says. H e suggests that the way the heme iron is tethered to the P450 enzyme is key: Most heme enzymes use a histidine to coord i n a t e iron. But P450s'cysteine thiolate linkage donates electron density to the ferryl group, making the oxo moiety more basic and ensuring that the species is protonated at p H values lower than 8.2, his team finds. "This is a key contribution to the ongoing debate about the mechanism of P450," says chemistry professorJames M. Mayer of the University of Washington, Seattle. His early studies of synthetic model systems indicate that the reactivity of ferryl species depends on both their redox potential and the ease with which their reduced forms can be protonated. So because the electron-donating thiolate linkage makes it easier to protonate the ferryl species, P450s can rely on ferryl radicals whose redox potentials are lower than what would normally be required to hydroxylate inert hydrocarbon substrates, Green says. "Such species, while capable ofhydroxylating normally inert saturated hydrocarbons, are less likely to oxidize the enzyme itself," he adds.-AMANDAYARNELL HTTP://WWW.CEN-ONLINE.ORG
