A Molecular Phone at Work

Researchers from the Department of Atomic Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) of the Center for Free Electron Laser Science in Hamburg, University of Potsdam (both in Germany) and the University of Toronto (Canada) have reconstructed a detailed chronological film revealing all the main stages of the catalytic cycle of an enzyme. Surprisingly, the communication between the protein units is carried out via a water network related to a corded telephone. This communication is aligned with a "breathing" movement, that is, the expansion and contraction of the protein. This temporal sequence of structures reveals dynamic movements as a fundamental element of the molecular foundations of biology.

All life is dynamic, as are its molecular building blocks. The motions and structural changes of biomolecules are essential to their functions. However, understanding these dynamic movements at the molecular level is a major challenge. How can a protein accelerate a chemical reaction, which would take years to unfold without help?

To this end, researchers turned to an enzyme that breaks the strongest single bond in organic chemistry: the C-F bond. Fluorinated carbons can be found in materials such as Teflon or GoreTex, as well as in many pharmaceuticals and pesticides. Fluorinated compounds have a particular influence on climate change, exceeding the effectiveness of CO₂in order of magnitude. As a result, the ability to better understand and possibly control the turnover of C-F bonds is of particular interest for climate change and bioremediation.

Researchers used time-resolved X-ray crystallography to take molecular snapshots during the reaction of this natural enzyme at physiological temperatures. This accelerated film revealed eighteen time points from 30 milliseconds to 30 seconds, covering all key catalytic states leading to C-F bond failure. Surprisingly, the film also shows that the enzyme "breathes" during rolling, that is, it expands and contracts in an aligned manner with the catalytic substeps.

Strikingly, the two halves of the enzyme communicate with each other via a chain of water molecules that connects the two halves. This water network allows the two halves to "talk to each other" and share information about their catalytic state. This is crucial for the function of the enzyme because only half of the enzyme can be active at any given time.

These dynamic changes have proved crucial for the function of the enzyme. Researchers expect many other systems to use similar mechanisms for their activities.