Enzyme mechanics win chemistry Nobel.

People often refer to enzymes as part of a cell's biochemical "machinery" because their hard labor keeps the cell in working order. Three scientists share this year's Nobel Prize in Chemistry for their insights into just how apt that comparison is.

Paul D. Boyer of the University of California, Los Angeles and John E. Walker of the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, were recognized for their research on an enzyme that acts as a molecular motor, and Jens C. Skou of Aarhus University in Denmark was honored for his discovery of an enzyme that works as a molecular pump.

Boyer and Walker study the enzyme ATP synthase, which manufactures ATP, the energy-storing molecule that fuels numerous biochemical reactions in the cell. In a series of studies in the 1970s, Boyer proposed an unusual mechanism for ATP synthase before its complete structure was known. He suggested that the enzyme rotates like a wheel, causing structural changes during each turn. These changes influence the enzyme's ability to bind the chemical precursors of ATP, catalyze their reaction, and release ATP into the cell (SN: 3/22/97, p. 173).

The mechanism "was extremely controversial when it was first enunciated, and now we take it in stride," says Steven M. Block of Princeton University. "I'm absolutely thrilled for Paul Boyer, who was a voice in the wilderness for a long time about this."

Walker's research on ATP synthase, begun in 1980 and reported in 1994, helped verify Boyer's model. "Walker accomplished the Herculean task of sequencing all the genes for the proteins in the enzyme and also determined the structure for part of it," says Richard L. Cross of the State University of New York Health Science Center at Syracuse. The catalytic part of the enzyme resembles a pumpkin with a stalk protruding from its center; a cylindrical part guides the flow of protons that powers rotation of the stalk.

Skou was recognized for his 1957 discovery of sodium-and potassium-stimulated ATPase, an enzyme that pumps those ions across cell membranes. The enzyme maintains different ion concentrations on either side of a membrane, a crucial factor in keeping the volume of a cell constant and propagating nerve signals. Many other ion pumps have since been discovered, including the enzymes responsible for muscle contraction and the production of stomach acid.

"These people are richly deserving of the prize," says Block. Regarding ATP synthase, he notes that "man, in his hubris, thought that he had invented the wheel. In fact, the wheel was one of nature's earliest inventions. It wasn't until the 1970s that we discovered that rotary mechanisms exist in biology."