Structure of enzyme against chemical warfare agents determined

January 28, 2009

The enzyme DFPase from the squid Loligo vulgaris, is able to rapidly and efficiently detoxify chemical warfare agents such as Sarin, which was used in the Tokyo subway attacks in 1995.

A detailed understanding of the mechanism by which enzymes catalyze chemical reactions is necessary for efforts aiming to improve their properties. A group of researchers at the University of Frankfurt, the Bundeswehr Institute for Pharmacology and Toxicology in Munich, and Los Alamos National Laboratory in New Mexico, USA, have successfully determined the structure of DFPase using neutron diffraction. They report their findings in the 20 January 2009 issue of the journal Proceedings of the National Academy of Sciences (106(3), 713-718).

The team used the neutron source at Los Alamos National Laboratory, one of only three sources worldwide equipped for protein crystallography. In contrast to structure determination using X-rays, neutrons are able to locate the positions of hydrogen atoms, which make up half of all atoms in proteins, and are crucial for chemical reactions. As X-rays interact with the electron cloud around an atomic nucleus, so heavier elements are more easily seen, while neutrons interact with the atomic nuclei, and atoms in proteins such as hydrogen, oxygen, nitrogen, carbon, and sulfur, all scatter neutrons in a similar manner. Yet despite being so widespread, hydrogen atoms in proteins are quite elusive.

As X-rays interact with the electron cloud around an atomic nucleus, hydrogen atoms, with only one electron, are normally invisible in structures. In contrast, neutrons interact with the atomic nuclei, such that atoms in proteins, hydrogen, oxygen, nitrogen, carbon, and sulfur, all scatter neutrons in a similar manner. The two techniques therefore yield complementary information about a protein structure. This information about hydrogen atoms is therefore essential for a basic understanding of the reaction mechanism of DFPase.

Neutron structures of proteins are quite rare and technically demanding, requiring large crystals and long measurement times. Though the first neutron structure of a protein was reported 40 years ago, in 1969, to date only about 20 unique structures have been solved, out of 50000 entries in the Protein Data Bank. " The effort has been absolutely worth it, " says Junior-Prof. Julian Chen, who published this work together with Dr. Marc-Michael Blum and Prof. Heinz Rueterjans. " Based on the results of this study, we can now create targeted changes to DFPase to augment the activity, as well as diversify the substrate range of the enzyme."

Source: Goethe University Frankfurt

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