FTIR Spectroscopy Enables Research at Subatomic Level

With the aid of Fourier Transform Infrared (FTIR) spectroscopy and computer simulations, the mechanism that causes the proteins that control critical bodily processes to be switched off has been analyzed and described at a subatomic level.

Researchers from Ruhr-University Bochum (RUB) used time-resolved FTIR spectroscopy to monitor enzymatic processes label-free at a high temporal and spatial resolution in their natural state, and to provide rate constants and structural information that were coded into IR spectra. To extract information about the precise location in the enzyme where a process took place, they used quantum-mechanical computer simulations of structural models.

They continue to bring new details of GTP hydrolysis to light: Klaus Gerwert, Carsten Kötting and Daniel Mann. Courtesy of RUB, Marquard.

“By combining theory and experiment, we thus gain a microscope with subatomic resolution,” explained researcher Klaus Gerwert.

Bonded to the proteins, the energy molecule Guanosine-5'-triphosphate (GTP) is crucial for turning off many protein switches. If an enzyme cleaves a phosphate group from GTP, the protein switch is turned off. This so-called GTP hydrolysis takes place within seconds and is activated by a specific amino acid, named the arginine finger. If the process fails, the patient could develop a disease.

Using a combination of FTIR spectroscopy and biomolecular simulations, the researchers were able to visualize the state of the arginine finger bonded to the GTP molecule at one hundredth of the atomic diameter, leading them to discover in detail how GTP hydrolysis is accelerated.

“Our long-term aim is for our basic research to contribute to the development of drugs for the treatment of cancer and severe genetic diseases,” said researcher Daniel Mann.

The research was published in Proceedings of the National Academy of Sciences (PNAS) (doi: 10.1073/pnas.1612394113).