DNA nanotechnology places enzyme catalysis within an arm's length

PUBLIC RELEASE DATE:

25-May-2014

Contact: Joe Caspermeyer joseph.caspermeyer@asu.edu 480-258-8972 Arizona State University

Using molecules of DNA like an architectural scaffold, Arizona State University scientists, in collaboration with colleagues at the University of Michigan, have developed a 3-D artificial enzyme cascade that mimics an important biochemical pathway that could prove important for future biomedical and energy applications.

The findings were published in the journal Nature Nanotechnology. Led by ASU Professor Hao Yan, the research team included ASU Biodesign Institute researchers Jinglin Fu, Yuhe Yang, Minghui Liu, Professor Yan Liu and Professor Neal Woodbury along with colleagues Professor Nils Walter and postdoctoral fellow Alexander Johnson-Buck at the University of Michigan.

Researchers in the field of DNA nanotechnology, taking advantage of the binding properties of the chemical building blocks of DNA, twist and self-assemble DNA into ever-more imaginative 2- and 3-dimensional structures for medical, electronic and energy applications.

In the latest breakthrough, the research team took up the challenge of mimicking enzymes outside the friendly confines of the cell. These enzymes speed up chemical reactions, used in our bodies for the digestion of food into sugars and energy during human metabolism, for example.

"We look to Nature for inspiration to build man-made molecular systems that mimic the sophisticated nanoscale machineries developed in living biological systems, and we rationally design molecular nanoscaffolds to achieve biomimicry at the molecular level," Yan said, who holds the Milton Glick Chair in the ASU Department of Chemistry and Biochemistry and directs the Center for Molecular Design and Biomimicry at the Biodesign Institute.

With enzymes, all moving parts must be tightly controlled and coordinated, otherwise the reaction will not work. The moving parts, which include molecules such as substrates and cofactors, all fit into a complex enzyme pocket just like a baseball into a glove. Once all the chemical parts have found their place in the pocket, the energetics that control the reaction become favorable, and swiftly make chemistry happen. Each enzyme releases its product, like a baton handed off in a relay race, to another enzyme to carry out the next step in a biochemical pathway in the human body.

For the new study, the researchers chose a pair of universal enzymes, glucose-6 phosphate dehydrogenase (G6pDH) and malate dehydrogenase (MDH), that are important for biosynthesismaking the amino acids, fats and nucleic acids essential for all life. For example, defects found in the pathway cause anemia in humans. "Dehydrogenase enzymes are particularly important since they supply most of the energy of a cell", said Walter. "Work with these enzymes could lead to future applications in green energy production such as fuel cells using biomaterials for fuel."

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DNA nanotechnology places enzyme catalysis within an arm's length

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