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    Danny Huang, PhD, Min Zhuang, Harold Hunt, Brenda Schulman, PhD

    Chemical switch triggers critical cell activities

    The freeze-frame image of a molecular relay race—in which one enzyme passes off a protein like a baton to another enzyme—illustrates how cells control some vital functions, according to a team of St. Jude investigators.

    A report on this work appears in the January 14 advanced online publication issue of Nature. The St. Jude discovery explains how a simple chemical link between molecules called a thioester bond works like a baton in a relay race, controlling the handoff of the NEDD8 protein from one enzyme to another. In the cell, this NEDD8 relay race triggers a number of biochemical reactions, one of which takes the brakes off cell division, allowing cells to multiply. These thioester bonds are chemical links between two biological molecules that form when a sulfur atom on one of the molecules binds to an atom that is part of the other molecule.

    Understanding how the thioester bond switch works is important not only because it explains a critical step in the NEDD8 handoff of one enzyme to the next, but also because similar enzymes run relays with other important protein batons, said Brenda Schulman, PhD, Structural Biology and Genetics and Tumor Cell Biology. “Our study shows that this simple switch could control comparable relays in charge of several different biochemical activities that keep cells alive and functioning normally,” said Schulman, a Howard Hughes Medical Institute (HHMI) investigator. Schulman is senior author of the Nature report.

    The researchers made a freezeframe image of this process using a technique called X-ray crystallography.

    In X-ray crystallography, scientists bombard crystals of proteins with X-rays and use the patterns formed by beams bouncing off the crystals to create computer-generated, 3-D images of the molecules.

    Other St. Jude authors of this paper are Danny Huang, PhD, Harold Hunt and Min Zhuang, Structural Biology and Genetics and Tumor Cell Biology. Huang is also an HHMI associate, and Zhuang is a graduate student from the University of Tennessee’s Interdisciplinary Program.

    February 2007