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The structure of an enzyme that neutralizes chemical warfare agents has been determined

The DFPase enzyme is capable of quickly and efficiently neutralizing chemical warfare agents such as Sarin, which was used in the Tokyo subway attack in 1995.

A sign warning against chemical weapons. From Wikipedia
A sign warning against chemical weapons. From Wikipedia

The DFPase enzyme is capable of quickly and efficiently neutralizing chemical warfare agents such as Sarin, which was used in the Tokyo subway attack in 1995. A detailed understanding of the exact mechanism by which enzymes catalyze chemical reactions is essential if we want to improve their properties.

A group of researchers from the University of Frankfurt, from the Institute of Pharmacology and Toxicology in Munich and from the Los Alamos National Laboratory in New Mexico, USA, were able to determine the three-dimensional structure of the enzyme by the "neutron diffraction" method.

The team used the neutron source at Los Alamos National Laboratory, one of only three sources worldwide suitable for protein crystallography. Contrary to the determination of structure by X-rays, the neutrons are able to locate the exact position of hydrogen atoms, which make up about half of the atoms in proteins and are essential for chemical reactions. X-rays react with the "cloud" of electrons surrounding the nuclei of atoms, so it is easier to detect heavy elements, while neutrons react with the nuclei of atoms, and the different types of atoms in proteins, such as hydrogen, oxygen, nitrogen, carbon and sulfur all react in a similar way.

However, despite their wide distribution, hydrogen atoms in proteins are quite elusive. Since X-rays react with the electron cloud surrounding the atom's nucleus, hydrogen atoms, which have only one electron, are usually almost invisible with this method of structure determination. Therefore, combining the data from both methods together provides comprehensive information about the structure of a protein. This information regarding the position of the hydrogen atoms is essential, therefore, for a basic understanding of the mechanism of activity of this enzyme and similar ones.

Determining protein structures using neutrons is quite rare and technically demanding, it requires large crystals and long measurement times. Although determining the structure of a protein with the help of neutrons was already reported forty years ago - in 1969, to date only about twenty unique structures of proteins have been deciphered, out of about fifty thousand that exist in the protein database.

"The effort was absolutely worth it," says Professor Julian Chen, who published this study together with Dr. Marc-Michael Blum and Professor Heinz Rueterjans. "Based on the findings of this study, we are now able to introduce controlled changes to the DFPase enzyme in order to increase its activity as well as to expand the range of substrates it is able to react with."
This study was published in the twentieth issue of January this year in the scientific journal Proceedings of the National Academy of Sciences (106(3), 713-718).

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